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Background: The aim of the present parallel clinical study is to evaluate the efficacy of 3D-printed biopolymers compounded with osteoconductive material (beta-tricalcium phosphate and hydroxyapatite) for soft tissue closure after tooth extraction., Materials and Methods: this study followed the CONSORT reporting guidelines; 39 patients were treated with socket preservation using 3D-printed biopolymers and randomly divided into 3 groups (Test 1, Test 2, and Control). All cases were treated without flap elevation, careful cleaning and debridement of the sites, and then randomly sealed as follows: In T1, with a 3D-printed disk of poli-D-lactic acid with 10% of hydroxyapatite; in T2, using a 3D-printed disk of poli-ε caprolactone with 20% of β-tricalcium phosphate; and in T3, the socket was left open to heal. At baseline (extraction time) and 6 weeks after extraction, the rate of exposure was evaluated and stratified according to the site (anterior, posterior)., Results: No dropouts were observed during the 6 weeks follow-up. All sites underwent uneventful healing with no complications. For posterior teeth, Test 1 and Test 2 showed full healing of the soft tissues with a reduction of the exposed area from 46.5 ± 8.25 mm 2 to 0.6 ± 0.84 mm 2 and from 47.1 ± 8.67 mm 2 to 0.6 ± 0.7 mm 2 , respectively. The Control group exhibited a reduction from 45.6 ± 7.25 mm 2 to 1.2 ± 0.9 mm 2 . Both Tests 1 and 2, when compared to the Control group, showed statistically significant better healing ( p < 0.05). Anterior teeth showed a complete closure of the socket 4 weeks after the extraction with no noticeable differences between Test and Control., Conclusions: Both materials used in this study showed evidence to achieve the purpose. Ethical Guidelines: written informed consent was obtained from the participants of the study, as requested by the Ethics Committee for Health Research Faculty of Dentistry, Universitas Trisakti, with the following number: 641/S3/KEPK/FKG/5/2023.

Objective: Patients with thromboembolic problems, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to examine the bleeding durations associated with various anticoagulants and antiplatelets during professional dental hygiene sessions, utilizing a modified Ivy test adapted for the oral context., Materials and Methods: Ninety-three consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn's post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc; RESULTS: Control patients presented the lowest bleeding time 50 s, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p = 0.004), VKA (p < 0.001), DAPT (p < 0.001)., Conclusions: Based on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT., Clinical Significance: bleeding did not interfere with the oral hygiene session The optimal period for dental treatment of these patients should be 2-3 h before the next dose, without the need to temporarily suspend the medication., (© 2024. The Author(s).)

Objective: To investigate whether cerebral autoregulation is impaired after neonatal cardiac surgery and whether changes in autoregulation metrics are associated with different congenital heart defects or the incidence of postoperative neurologic events., Methods: This is a retrospective observational study of neonates undergoing monitoring during the first 72 hours after cardiac surgery. Archived data were processed to calculate the cerebral oximetry index (COx) and derived metrics. Acute neurologic events were identified by an electronic medical record review. The Skillings-Mack test and the Wilcoxon signed-rank test were used to analyze the evolution of autoregulation metrics over time; the Mann-Whitney U test was used for comparison between groups., Results: We included 28 neonates, 7 (25%) with hypoplastic left heart syndrome and 21 (75%) with transposition of the great arteries. Overall, the median percentage of time spent with impaired autoregulation, defined as percentage of time with a COx >0.3, was 31.6% (interquartile range, 21.1%-38.3%). No differences in autoregulation metrics between different cardiac defects subgroups were observed. Seven patients (25%) experienced a postoperative acute neurologic event. Compared to the neonates without an acute neurologic event, those with an acute neurologic event had a higher COx (0.16 vs 0.07; P = .035), a higher percentage of time with a COx >0.3 (39.4% vs 29.2%; P = .017), and a higher percentage of time with a mean arterial pressure below the lower limit of autoregulation (13.3% vs 6.9%; P = .048)., Conclusions: COx monitoring after cardiac surgery allowed for the detection of impaired cerebral autoregulation, which was more frequent in neonates with postoperative acute neurologic events., Competing Interests: Conflict of Interest Statement P.S. reported receiving licensing fees for ICM+ software, licensed by Cambridge Enterprise Ltd, University of Cambridge. A.M. reported serving on an advisory board for Air Liquide for the administration of iNO in cardiac surgery. C.R. reported consulting fees from Masimo. E.B. reported support from the Medical Research Council (Grant MR N013433-1) and the Gates Cambridge Scholarship. G.R.B. has been supported in part by the MacCutcheon Family Foundation (grant No. 44607). The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Professional oral hygiene is essential to prevent peri-implant disease. Appropriate instruments should be employed for implant-supported restorations: they should effectively remove deposits without damaging dental implant surface. The aim of the present systematic review is to investigate the efficacy and safety of erythritol air-polishing in implant-supported rehabilitations, compared to alternative hygienic techniques., Materials and Methods: The guidelines reported in the indications of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) were employed for this systematic review. The focused question was: 'what is the effect of erythritol air-polishing on dental implant surfaces regarding its cleansing efficacy and/or safety?' The final online search was conducted on 13 August 2023; MEDLINE-PubMed, Scopus and Cochrane Library were employed. Comparative in vitro or in vivo original studies were included., Results: The initial database search yielded 128 entries; the final selection comprised 15 articles. The risk of bias was evaluated using the Newcastle Ottawa scale (NOS), the Cochrane Handbook for Systematic Reviews of Interventions, GRADE method. Ultrasonic scaling with PEEK tips, glycine air-polishing and cold atmospheric plasma were the devices most frequently compared to erythritol powder in the included studies. Erythritol air-polishing appeared to be significantly more effective in reducing biofilm compared to other treatments, without causing any significant damage to the implant surface and peri-implant tissues, promoting a good biological response., Conclusion: Erythritol air-polishing showed promising results for professional oral hygiene in implant-supported restorations. According to this systematic review, it is effective and safe for removing biofilm from titanium dental implants., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Coaxial implants with an inclined neck might overcome some problems related to angulation of the implant axis when using tilted implants. Therefore, the aim of the present work was to conduct a narrative review of the current literature and to present a case series comparing traditional and coaxial external hex implants in full-arch immediate loading rehabilitations of the maxilla. Methods: A total of 13 external hex tapered implants (Southern Implants) was inserted in the upper jaw of 3 patients. Each patient received two tilted implants in distal sites. In one randomly selected quadrant, the tilted implant was a standard implant, while a Co-Axis ® implant with a 24° inclination of the implant shoulder was inserted on the other hemi-arch. Straight conical abutments were screwed on coaxial implants while multiunit abutments of appropriate inclination were screwed as needed on the other implants to correct their axes. Peri-implant bone level was recorded radiographically at T0 (delivery of the immediate loading prosthesis), and at 3, 6, 12, and 24 months of healing and then annually. Plaque index, probing depth, and bleeding on probing were also evaluated. Cumulative implant survival rate (CSR) was calculated, and biological or technical complications were recorded as well as the operator satisfaction towards the use of coaxial implants. Results : The preliminary data collected did not show significant differences in peri-implant tissues health and maintenance over time between the two implant types. No implants failed, and both implant types proved to be favorable for full-arch rehabilitation using tilted implants. Coaxial implants facilitated the prosthodontic procedures. However, a learning curve is required in order to optimize their insertion. Conclusions: Both implants proved to be reliable and suitable for achieving clinical success in full-arch immediate loading rehabilitations, but further research with longer follow-up and larger sample size is needed to confirm these preliminary outcomes.

Background: Childhood cancer survivors (CCS), of whom there are about 500,000 living in Europe, are at an increased risk of developing health problems [1-6] and require lifelong Survivorship Care. There are information and knowledge gaps among CCS and healthcare providers (HCPs) about requirements for Survivorship Care [7-9] that can be addressed by the Survivorship Passport (SurPass), a digital tool providing CCS and HCPs with a comprehensive summary of past treatment and tailored recommendations for Survivorship Care. The potential of the SurPass to improve person-centred Survivorship Care has been demonstrated previously [10,11]., Methods: The EU-funded PanCareSurPass project will develop an updated version (v2.0) of the SurPass allowing for semi-automated data entry and implement it in six European countries (Austria, Belgium, Germany, Italy, Lithuania and Spain), representative of three infrastructure healthcare scenarios typically found in Europe. The implementation study will investigate the impact on person-centred care, as well as costs and processes of scaling up the SurPass. Interoperability between electronic health record systems and SurPass v2.0 will be addressed using the Health Level Seven (HL7) International interoperability standards., Results: PanCareSurPass will deliver an interoperable digital SurPass with comprehensive evidence on person-centred outcomes, technical feasibility and health economics impacts. An Implementation Toolkit will be developed and freely shared to promote and support the future implementation of SurPass across Europe., Conclusions: PanCareSurPass is a novel European collaboration that will improve person-centred Survivorship Care for CCS across Europe through a robust assessment of the implementation of SurPass v2.0 in different healthcare settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: To evaluate peri-implant tissue health and bone resorption in patients with implant-supported fixed partial rehabilitations. In particular, possible correlations between plaque accumulation and bone loss, as well as other periimplant health parameters, were investigated., Materials and Methods: A total of 44 patients rehabilitated with fixed implant-supported partial rehabilitations were included. The following parameters were recorded: spontaneous bleeding (SB), suppuration, bleeding on probing (BOP), plaque index (PI), and probing depth (PD). Periapical radiographs were taken to measure crestal bone loss (BL). A nonparametric test (Spearman rank coefficient; rs) was used to identify possible correlations between the clinical parameters recorded., Results: A total of 121 implants were analyzed. Global PI and BOP were 49.58% and 20.25%, respectively. There were no cases of suppuration, and only 2 implants showed spontaneous bleeding. Mean BL was 1.53 mm (SD: 0.98). No implants showed peri-implantitis. There was a weak, statistically significant correlation between PI and BL (rs = 0.27, P [2-tailed] = .99) and between PI and the other peri-implant parameters (BOP: rs = 0.14, P = .14; PD: rs = 0.04, P = .65; SB: rs = -0.08, P = .34). A very weak correlation was also found between BL and BOP (rs = 0.1, P = .2) and between BL and PD (rs = 0.02, P = .7). Correlation was found between BL and age (rs = 0.13, P = .81) and between the other peri-implant parameters and age using dichotomization (> or < 65 years; PI: rs = -0.14, P = .11; PD: rs = -0.21, P = .01; BOP: rs = -0.21, P = .01; SB: rs = 0.05, P = .53). No statistically significant correlations were found between the clinical parameters evaluated and the sex or the dental arch treated (maxilla vs mandible). In contrast, the correlation between periodontal parameters and years elapsed since surgery (follow-up) was significant., Conclusions: The present research suggests that in implant-supported fixed partial rehabilitations, dental implants with greater plaque accumulation are more likely to present augmented probing depth, peri-implant inflammation, and bone loss, although the correlation is statistically very weak. Patient age and time of follow-up also significantly affected peri-implant health parameters.

Background: Restorative materials might significantly affect load transmission in peri-implant bone. The aim of the present study is to evaluate the shock absorption capacity of two different polymeric materials to be used for implant-supported prostheses., Methods: A masticatory robot was used to compare the shock absorption capacity of veneered and non-veneered polyetherketoneketone (PEKK), Pekkton ® ivory (Cendres+Mètaux), and the glass fiber-reinforced composite (GFRC), TRINIA TM (Bicon). Five identical sample crowns for each of the three groups were tested. Forces transmitted at the simulated peri-implant bone were recorded and statistically analyzed., Results: The statistical analysis of forces transmitted at the simulated dental implant revealed significant differences between the materials tested and between these materials and zirconia, glass ceramic, composite resin, and acrylic resin. Only differences between PEKK and veneered PEKK and between PEKK and one of the previously tested composite resins were not statistically significant. PEKK samples demonstrated significantly greater shock absorption capacity compared to GFRC., Conclusions: PEKK revealed optimal shock absorption capacity. Further studies are needed to evaluate its efficacy in the case of long-span prostheses with reduced prosthetic volume.

Background: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort., Methods: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940-2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated., Results: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50., Discussion: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms., (© 2024. The Author(s).)

Purpose: To investigate the possible antimicrobial activity of glycine air polishing by comparing peri-implant microbiota before and after treatment., Materials and Methods: A total of 15 patients who received implant-supported full-arch fixed rehabilitations were included. After prosthesis removal (T0), Plaque Index (PI), probing depth (PD), and bleeding on probing (BOP) were recorded. In each hemiarch, the implant with the highest PD score was selected for microbiologic sample collection from the peri-implant sulcus (T0). All patients received two different hygienic protocols (randomly administered, one per each hemiarch): glycine air-polishing (G) and cleansing with cotton pellets soaked in saline (C). At 7 days (T1) and 3 months (T2) after the intervention, PI and BOP were recorded, and new microbiologic samples were taken. Traditional polymerase chain reaction (PCR) and quantitative PCR real-time were employed for microbiologic analysis to investigate how the presence of different bacterial species varied according to the hygienic treatment performed., Results: Treatment G provided a significantly higher PI score reduction around implants compared to treatment C (P = .015). No statistical difference was found in the microbial population around G and C implant sites, with Tannerella forsythia being the most commonly detected bacterial species in both G and C groups. No statistical differences were found between the antimicrobial activity of treatments C and G., Conclusions: Glycine powder air polishing is a valid method for professional hygienic care of implants and was more effective in PI reduction compared to the control treatment. However, its antimicrobial efficacy cannot be confirmed by the outcomes of the present study.

Purpose: Childhood cancer survivors are at the risk of developing subsequent colorectal cancers (CRCs), but the absolute risks by treatment modality are uncertain. We quantified the absolute risks by radiotherapy treatment characteristics using clinically accessible data from a Pan-European wide case-control study nested within a large cohort of childhood cancer survivors: the PanCareSurFup Study., Methods: Odds ratios (ORs) from a case-control study comprising 143 CRC cases and 143 controls nested within a cohort of 69,460 survivors were calculated. These, together with standardized incidence ratios for CRC for this cohort and European general population CRC incidence rates and survivors' mortality rates, were used to estimate cumulative absolute risks (CARs) by attained age for different categories of radiation to the abdominopelvic area., Results: Overall, survivors treated with abdominopelvic radiotherapy treatment (ART) were three times more likely to develop a subsequent CRC than those who did not receive ART (OR, 3.1 [95% CI, 1.4 to 6.6]). For male survivors treated with ART, the CAR was 0.27% (95% CI, 0.17 to 0.59) by age 40 years, 1.08% (95% CI, 0.69 to 2.34) by age 50 years (0.27% expected in the general population), and 3.7% (95% CI, 2.36 to 7.80) by age 60 years (0.95% expected). For female survivors treated with ART, the CAR was 0.29% (95% CI, 0.18 to 0.62) by age 40 years, 1.03% (95% CI, 0.65 to 2.22) by age 50 years (0.27% expected), and 3.0% (95% CI, 1.91 to 6.37) by age 60 years (0.82% expected)., Conclusion: We demonstrated that by age 40 years survivors of childhood cancer treated with ART already have a similar risk of CRC as those age 50 years in the general population for whom population-based CRC screening begins in many countries. This information should be used in the development of survivorship guidelines for the risk stratification of survivors concerning CRC risk.

Purpose: Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy., Methods: Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship., Results: The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation ( P trend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m 2 , the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer., Conclusion: To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m 2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.

Purpose: To retrospectively evaluate the clinical outcomes of immediately loaded zygomatic implants combined with anterior regular implants (hybrid zygoma) for the fixed rehabilitation of atrophic maxillae. Materials and Methods: A total of 18 patients were enrolled in this study and treated with the hybrid zygoma concept by an experienced surgeon. Follow-up visits were planned after 1 week, 3 weeks, 4 months, 6 months, then annually. At the last follow-up appointment (mean: 36 months after surgery; range: 24 to 52 months), the prostheses were unscrewed and the implants and peri-implant tissues were examined. The primary outcome evaluated was implant success. Following the criteria proposed by Aparicio et al, implant success was classified in five grades, with grade I representing the best condition and grade V representing a failure. At the annual check-up, patients were asked to fill out a questionnaire to evaluate their satisfaction with their oral rehabilitation. Results: A total of 80 implants (34 zygomatic and 46 regular) were inserted. One zygomatic implant was lost in one patient, and two regular implants failed in two other patients. Of the zygomatic implants, 24 (70.6%) presented a success grade I, 9 (26.5%) a success grade II, and 1 (2.9%) a grade V. Sinusitis was the most common biologic complication, occurring in two patients (5.6%). Two patients showed unilateral upper lip paresthesia that was persistent at the last follow-up appointment. According to the annual follow-up visit questionnaire data, 72%, 89%, and 94% of patients declared that they were satisfied with their phonetic ability, chewing ability, and esthetics, respectively. Conclusion: Although zygomatic implants combined with anterior regular implants present a higher risk of complications than traditional implantology, they allow for immediately loaded full-arch fixed rehabilitation of patients with advanced atrophy of the posterior maxilla, which provides satisfactory chewing ability, esthetics, and phonetics.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents an effective treatment for a variety of inborn errors of immunity (IEI). We report the experience of children affected by IEI who received allo-HSCT over a period of 32 years at IRCCS Istituto Giannina Gaslini, Genoa, Italy. HSCTs were performed in 67 children with IEI. Kaplan-Meier estimates of overall survival (OS) rate at 5 years in the whole group of patients was 83.4% after a median follow-up of 4 years. Median age at transplant was 2.5 years. Eight allo-HSCTs were complicated by either primary or secondary graft failure (GF), the overall incidence of this complication being 10.9%. Incidence of grade 3-4 acute GvHD (aGvHD) was 18.7%, significantly lower in the haploidentical transplant cohort ( p = 0.005). Year of transplant (≤2006 vs . >2006) was the main factor influencing the outcome. In fact, a significant improvement in 5-year OS was demonstrated (92.5% >2006 vs . 65% ≤2006, p = 0.049). Frequency of severe aGvHD was significantly reduced in recent years (≤2006 61.5%, vs . >2006 20%, p = 0.027). A significant progress has been the introduction of the TCR αβ/CD19-depleted haploidentical platform, which was associated with the absence of severe aGvHD. However, it was associated with 23.5% incidence of GF. All but one patient experiencing GF in the this specific cohort were successfully retransplanted. In summary, allo-HSCT is confirmed to be an effective treatment for children with IEI, even in the absence of an HLA-matched donor., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dell’Orso, Bagnasco, Giardino, Pierri, Ferrando, Di Martino, Micalizzi, Guardo, Volpi, Sabatini, Miano, Gattorno, Dufour and Faraci.)

Background: Survivors of Hodgkin lymphoma (HL) are at risk of developing non-Hodgkin lymphoma (NHL) after treatment; however, the risks of developing subsequent primary lymphomas (SPLs), including HL and NHL, after different types of childhood cancer are unknown. The authors quantified the risk of SPLs using the largest cohort of childhood cancer survivors worldwide., Methods: The Pan-European Network for Care of Survivors After Childhood and Adolescent Cancer (PanCare) Survivor Care and Follow-Up Studies (PanCareSurFup) cohort includes 69,460 five-year survivors of childhood cancer, diagnosed during 1940 through 2008, from 12 European countries. Risks of SPLs were quantified by standardized incidence ratios (SIRs) and relative risks (RRs) using multivariable Poisson regression., Results: Overall, 140 SPLs, including 104 NHLs and 36 HLs, were identified. Survivors were at 60% increased risk of an SPL compared with the general population (SIR, 1.6; 95% confidence interval [CI], 1.4-1.9). Survivors were twice as likely to develop NHL (SIR, 2.3; 95% CI, 1.9-2.8), with the greatest risks among survivors of HL (SIR, 7.1; 95% CI, 5.1-10.0), Wilms tumor (SIR, 3.1; 95% CI, 1.7-5.7), leukemia (SIR, 2.8; 95% CI, 1.8-4.4), and bone sarcoma (SIR, 2.7; 95% CI, 1.4-5.4). Treatment with chemotherapy for any cancer doubled the RR of NHL (RR, 2.1; 95% CI, 1.2-3.9), but treatment with radiotherapy did not (RR, 1.2; 95% CI, 0.7-2.0). Survivors were at similar risk of developing a subsequent HL as the general population (SIR, 1.1; 95% CI, 0.8-1.5)., Conclusions: In addition to HL, the authors show here for the first time that survivors of Wilms tumor, leukemia, and bone sarcoma are at risk of NHL. Survivors and health care professionals should be aware of the risk of NHL in these survivors and in any survivors treated with chemotherapy., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Monitoring antibiotic use in the pediatric population is a challenge, especially when determining a relationship between specific pathogens, infections, and antibiotic use. We retrospectively analyzed the consumption of anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs from 2017 to 2021 at Istituto Giannina Gaslini by means of defined daily dose (DDD) adopted for adults by World Health Organization. We observed a statistically significant increase in the use of daptomycin and ceftaroline, combined with a decrease in the use of vancomycin. In the same period, we observed an increase in the proportion of bloodstream infections due to MRSA with vancomycin minimally inhibitory concentration (MIC mg/L) = 1, that represented the 100% of cases in 2021. This aspect was combined with the observation that in the 59% of cases, where vancomycin plasma concentrations were evaluated, it was not possible to achieve a ratio of the 24-h area under the concentration-time curve and MIC (AUC 0-24 /MIC) of vancomycin ≥ 400 mg/L. This study confirms that DDD can be used in pediatrics to monitor antibiotic consumption in relationship with infections epidemiology. Moreover, it describes the presence of vancomycin MIC creep for MRSA also in pediatrics and the difficulties in obtaining effective vancomycin plasma concentrations in children.

Background: The aim of the present study was to investigate the accuracy of a new digital impression system, comparing it to the plaster impression technique in the realization of full-arch implant-supported metal frameworks., Methods: We took 11 scans (8 of the upper maxilla and 3 of the lower jaw) on a sample of nine patients previously rehabilitated with fixed full-arch screw-retained prostheses following the Columbus Bridge Protocol (CBP) with four to six implants (total: 51) since at least 4 months. Two impressions were taken for each dental arch: one analogic plaster impression using pick-up copings and an open tray technique and a second one using an intra-oral scanner. Two milled metal substructures were realised. The precision and passivity of the substructures were clinically analysed through the Sheffield test and endo-oral radiographs. Laboratory scans of the plaster casts obtained from an intra-oral scanner (IOS) and of the plaster casts obtained from traditional impression were compared with the intraoral scans following Hausdorff's method and an industrial digital method of optical detection to measure discrepancies. A Mann-Whitney test was performed in order to investigate average distances between surfaces after the superposition., Results: The Sheffield test demonstrated an excellent passivity of the frameworks obtained through both the digital and the analogic method. In 81.81% of cases (n = 9) both substructures were found to have a perfect fit with excellent passivity, while in 18.18% (n = 2) of cases the substructures were found to have a very slight discrepancy. From the radiographic examination, no gaps between the frameworks and the implant heads or multiunit abutments were observed, with 100% accuracy. By superimposing digital files of scans according to Hausdorff's method, a statistically significant discrepancy ( p = 0.006) was found between the digital scans and the digital models obtained from plaster impressions. Three-dimensional optical detection found a mean discrepancy of 0.11 mm between the analogic cast and the cast derived from the digital impression., Conclusions: The present study clinically demonstrates that milled implant-supported full-arch frameworks obtained through a digital scan and the herein described technique have an accuracy comparable to those obtained with traditional plaster impression.

Purpose: Heart failure (HF) is a potentially life-threatening complication of treatment for childhood cancer. We evaluated the risk and risk factors for HF in a large European study of long-term survivors. Little is known of the effects of low doses of treatment, which is needed to improve current treatment protocols and surveillance guidelines., Methods: This study includes the PanCareSurFup and ProCardio cohort of ≥ 5-year childhood cancer survivors diagnosed between 1940 and 2009 in seven European countries (N = 42,361). We calculated the cumulative incidence of HF and conducted a nested case-control study to evaluate detailed treatment-related risk factors., Results: The cumulative incidence of HF was 2% (95% CI, 1.7 to 2.2) by age 50 years. The case-control study (n = 1,000) showed that survivors who received a mean heart radiation therapy (RT) dose of 5 to < 15 Gy have an increased risk of HF (odds ratio, 5.5; 95% CI, 2.5 to 12.3), when compared with no heart RT. The risk associated with doses 5 to < 15 Gy increased with exposure of a larger heart volume. In addition, the HF risk increased in a linear fashion with higher mean heart RT doses. Regarding total cumulative anthracycline dose, survivors who received ≥ 100 mg/m 2 had a substantially increased risk of HF and survivors treated with a lower dose showed no significantly increased risk of HF. The dose-response relationship appeared quadratic with higher anthracycline doses., Conclusion: Survivors who received a mean heart RT dose of ≥ 5 Gy have an increased risk of HF. The risk associated with RT increases with larger volumes exposed. Survivors treated with < 100 mg/m 2 total cumulative anthracycline dose have no significantly increased risk of HF. These new findings might have consequences for new treatment protocols for children with cancer and for cardiomyopathy surveillance guidelines.

Background: Survivors of childhood cancer are at risk of subsequent primary malignant neoplasms (SPNs), but the risk for rarer types of SPNs, such as oral cancer, is uncertain. Previous studies included few oral SPNs, hence large-scale cohorts are required to identify groups at risks., Methods: The PanCareSurFup cohort includes 69,460 5-year survivors of childhood cancer across Europe. Risks of oral SPNs were defined by standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence., Results: One hundred and forty-five oral SPNs (64 salivary gland, 38 tongue, 20 pharynx, 2 lip, and 21 other) were ascertained among 143 survivors. Survivors were at 5-fold risk of an oral SPN (95% CI: 4.4-5.6). Survivors of leukaemia were at greatest risk (SIR = 19.2; 95% CI: 14.6-25.2) followed by bone sarcoma (SIR = 6.4, 95% CI: 3.7-11.0), Hodgkin lymphoma (SIR = 6.2, 95% CI: 3.9-9.9) and soft-tissue sarcoma (SIR = 5.0, 95% CI: 3.0-8.5). Survivors treated with radiotherapy were at 33-fold risk of salivary gland SPNs (95% CI: 25.3-44.5), particularly Hodgkin lymphoma (SIR = 66.2, 95% CI: 43.6-100.5) and leukaemia (SIR = 50.5, 95% CI: 36.1-70.7) survivors. Survivors treated with chemotherapy had a substantially increased risk of a tongue SPN (SIR = 15.9, 95% CI: 10.6-23.7)., Conclusions: Previous radiotherapy increases the risk of salivary gland SPNs considerably, while chemotherapy increases the risk of tongue SPNs substantially. Awareness of these risks among both health-care professionals and survivors could play a crucial role in detecting oral SPNs early., (© 2022. The Author(s).)

Statement of Problem: Limited information is available on the differences between tissue-level implants with an ultrathin threaded microsurface conical transmucosal portion and bone-level implants rehabilitated with conical custom abutments., Purpose: The purpose of this retrospective study was to assess the outcomes of crowns designed as per the biologically oriented preparation technique (BOPT) cemented on conical titanium abutments on tissue-level and bone-level implants., Material and Methods: Patients consecutively rehabilitated with a delayed loading protocol with anterior implant-supported single crowns with a feather-edge margin, in function for at least 4 years, were recruited and divided into 2 groups based on the implant type they had received: tissue-level implants with a conical transmucosal portion or bone-level implants rehabilitated with a conical abutment by following the platform switching concept. Bone resorption, pink esthetic score (PES), and white esthetic score (WES) were collected and analyzed. The nonparametric Mann-Whitney test was performed to analyze all parameters (α=.05 for all tests)., Results: A total of 43 participants (48 implants) were included in the present study. The mean follow-up period was 4.5 years (range 52-64 months). A statistically significant difference (P=.004) was found in the mean ±standard deviation bone resorption between tissue-level implants (0.38 ±0.46 mm) and bone-level implants (0.83 ±0.58 mm). Higher values for both PES and WES were obtained in the tissue-level implant group., Conclusions: Within the limitations of the present retrospective study, tissue-level implants with a conical transmucosal portion seem to provide a suitable alternative to bone-level implants in the anterior area., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

This article presents the international dataset of cases in which the association of Langerhans cell Histiocytosis (LCH) with other malignancies (AM) was documented occurring at any age before, concurrently or after LCH. These data are mostly derived from previously published manuscripts or from completed case report forms (CRFs) by Histiocyte Society (HS) members or colleagues. In particular, for each case of LCH-AM, the database reports all the available data about clinical and biologic characteristics of the two tumors, as well about treatment and status at follow-up. The AM were categorized as: i) leukemias [acute lymphoblastic or myeloid leukemia (ALL and AML, respectively), other leukemias] and myeloproliferative disorders; ii) lymphomas [Hodgkin lymphoma (HL) and non-Hodgkin lymphomas (NHL)] and iii) solid tumors. A total of 270 LCH-AM cases were documented, of which 116 (43%) occurred among children. After stratification by age at LCH diagnosis, using 18 years as cut-off between children and adults, we here provide details on the clinical characteristics in terms of LCH system involvement and affected organs, as well on the temporal relationship between the LCH and AM diagnoses, including details on the AM malignancy types. In 19 cases the LCH and the corresponding AM occurred in a different age group. The data set is available for future studies in view of new insights of the genetic or environmental determinants of LCH and/or of treatment related subsequent neoplasms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Inc.)

Purpose: The frequency of Langerhans cell histiocytosis (LCH) and associated malignancies (AM) is greater than statistically expected. Here, we analyze LCH-AM co-occurrence in both children and adults., Methods: Between 1991 and 2015, data were collected by regular questionnaires to members of the Histiocyte Society and searches in PubMed and Abstract Books. Patients were grouped by age at LCH diagnosis (≤ and &gt;18 years), and types and timing of AM occurrence were plotted with respect to the LCH diagnosis. For the statistical analysis, only the first AM were considered., Results: A total of 285 LCH-AM in 270 patients were identified, 116 (43%) ≤ 18 years, and 154 (57%) &gt;18 years. In childhood LCH-AM pairs, leukemias and myeloproliferative disorders (n = 58; 50.0%) prevailed over solid tumors (n = 43; 37.1%) and lymphoma (n = 15; 12.9%). In adults, solid tumors were reported in 61 patients (39.6%), lymphoma, and leukemias and myeloproliferative disorders in 56 (36.4%) and 37 (24.0%) patients, respectively. In most children, AM followed LCH (n = 69, 59.5%), whereas in adults, LCH and AM occurred concurrently in 69 patients (44.8%). In children, T-lineage acute lymphoblastic leukemia (ALL) and promyelocytic acute myeloid leukemia (AML) and retinoblastoma were over-represented and thyroid carcinoma in adults., Conclusions: The largest collection of data on LCH-AM to date clearly indicates inherent relationships between specific types of AM and LCH, which may be due to therapy effects, clonal evolution, and germ-line predisposition, respectively. Prospective thorough genetic analysis is warranted and will hopefully shed light on the association of LCH and second neoplasms., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents a valuable alternative for children with nonmalignant disease and ex vivo negative selection of TCR-αβ + cells is an emerging graft manipulation option that carries several potential advantages in terms of reduced risk of graft-versus-host disease (GvHD) and improved immune reconstitution. We report all consecutive patients with a diagnosis of nonmalignant disease who received a TCR-αβ + and CD19 + depleted haplo-HSCT at "IRCCS Istituto Giannina Gaslini" from 2013 to 2019; the conditioning regimen was myeloablative or non-myeloablative, depending on underlying disease; all patients received antithymocyte globulin and rituximab. No post-transplantation GvHD prophylaxis was given in presence of a TCR-αβ + cell dose in the graft lower than the threshold of 1 × 10 5 /kg of the recipient's weight. Among 20 HSCTs, engraftment occurred in 17 (85%) after a median of 14 and 12 days from graft infusion for neutrophils and platelets, respectively. Primary graft failure was diagnosed in 3 (15%) patients, and 2 (10%) experienced secondary rejection; all of these patients underwent a second HSCT. The cumulative incidence of a-GvHD and c-GvHD was 15% (2 = grade 1, 1 = grade 4) at 90 days and 5% (1 = grade 1) at 7 months, respectively. Cytomegalovirus reactivation requiring pre-emptive treatment was observed in 9 patients (45%). One patient developed a JC virus-related progressive multifocal leukoencephalopathy, successfully managed with donor-derived virus-specific T-cell infusions. A complete immunological recovery was reached in most patients within 6 months. After a median follow-up of 4 years, 18 patients are alive, with a cumulative survival probability of 90%. Haplo-HSCT after ex vivo TCR-αβ + /CD19 + negative selection may be considered a good option for children with nonmalignant diseases because it ensures a high engraftment rate with an acceptable risk of graft failure, very low incidence of significant GvHD, and good immune reconstitution with low frequency of severe virus-related disease. However, the control of viral infection/reactivation should be kept high to promptly provide pre-emptive treatments and approaches of antiviral adoptive immunotherapy., Competing Interests: Conflict of interest statement There are no conflicts of interest to report. Authorship statement: SG contributed to data collection, material preparation, analysis of results, and wrote the manuscript. SG, MF, and EL contributed equally to the study conception and to the patient's management. FB performed all statistical analyses. MR and MF contributed to donor selection and management. MP and FS managed the graft manipulation. MM, FP, GD, BC and MR contributed to data collection and to the clinical management of patients. All authors contributed to the manuscript revision and approved its final version., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose: To retrospectively evaluate the survival rate and technical and biologic complications of feather-edge zirconia and metal-ceramic implant restorations cemented on conical titanium abutments., Materials and Methods: Patients rehabilitated with implant-supported single crowns or fixed dental prostheses (FDPs) were divided into four groups: ZR-TL = tissue-level implant with a convergent collar and zirconia restoration; ZR-BL = bone-level implant and zirconia restoration; MC-TL = tissue-level implant with a convergent collar and metal-ceramic restoration; MC-BL = bone-level implant and metal-ceramic restoration. All of the restorations were cemented onto conical titanium abutments and had feather-edge margins, following the biologically oriented preparation technique (BOPT). Crown-level survival rates, technical and biologic complications, and bone resorption were registered. Chi-square test was performed to analyze all evaluated parameters among the groups. Nonparametric Mann-Whitney test was performed to analyze changes in bone level., Results: A total of 85 patients (133 implants, 66 single crowns, and 28 FDPs) were included in the present study with a mean follow-up time of 4.98 years. The overall survival rate was 98.2% for zirconia and 97.5% for metal-ceramic restorations at the crown level. No significant differences were found between the zirconia (ZR-BL and ZR-TL) and the metal-ceramic (MC-BL and MC-TL) groups for technical complications (P > .05). Bone resorption was 0.33 (0.37) mm in MC-TL; 0.61 (0.52) mm in MC-BL; 0.39 (0.51) mm in ZR-TL; and 0.77 (0.64) mm in ZR-BL, showing significantly greater bone loss in bone-level implants (P = .011)., Conclusion: Zirconia implant restorations with feather-edge margins seem to be a viable alternative in cases of both tissue-level and bone-level implants.

Objectives: The detrimental effect of tobacco smoking on periodontal health is well known, while the effect of electronic cigarette on periodontal parameters has been less investigated. The aim of the present systematic review was to compare periodontal indices in three categories of patients: traditional cigarette smokers (TS), e-cigarette smokers (ES), and non-smokers (NS)., Materials and Methods: An electronic search was conducted for studies published until December 2021 on MEDLINE (PubMed), ISI Web of Science, and Scopus. A hand search was additionally conducted. Clinical observational and cross-sectional trials investigating periodontal indices among tobacco smokers (TS), electronic cigarette smokers (ES) and non-smokers (NS) were included and selected by 2 independent reviewers. Data on probing depth (PD), plaque index (PI), and bleeding on probing (BOP) were collected. The risk of bias was evaluated according to the NIH quality assessment tool and a network meta-analysis (NMA) was undertaken., Results: Five relevant studies, from 707 identified, were included. Overall, 512 patients were included, of them 170 were NS, 176 were TS, and 166 were ES. A significant difference in the comparison among TS vs NS: effect size (ES) = 3.297 (95%CI: [2.142-4.454], p = 0.001) and TS and ES ES = 2.507 (95%CI: [1.351-3.663], p = 0.001) was identified for PD. A significant difference in the comparison among TS and NS, ES = 21.34 (95%CI: [13.41-29.27], p = 0.001) and between TS and ES ES = 15.67 (95%CI: [7.73-23.62], p = 0.001) was identified for PI. The analysis of BOP values shows a significant difference in the comparison among ES and NS: ES = - 16.22 (95%CI: [- 22.85 to - 9.59], p < 0.001) and between TS and NS: ES = - 14.47 (95%CI: [- 21.103 to - 7.848], p < 0.001). Based on the SUCRA ranking, NS showed the most favorable outcome for PD and PI, followed by ES. Tobacco smokers were clearly in the last position. Dealing with BoP ES showed the most favorable outcome, followed by TS. NS were in the last position., Conclusions: Periodontal parameters were similar among NS and ES, while TS presented the worst indices. BoP was reduced both in ES and in TS., Clinical Relevance: Results of the present review suggest a reduced effect on periodontal tissue of e-cig smoking compared to traditional cigarettes, despite recent studies proved that e-cig smoking increases oxidative stress, inflammatory responses, change in pulmonary cellular behavior, and stimulates DNA injury., (© 2022. The Author(s).)

Antibiotic resistance is an increasing problem, especially in children with urinary tract infections. Rates of drug-specific resistant pathogens were reported, and an easy prediction model to guide the clinical decision-making process for antibiotic treatment was proposed. Data on microbiological isolation from urinoculture, between January 2007−December 2018 at Istituto Gaslini, Italy, in patients aged <19 years were extracted. Logistic regression-based prediction scores were calculated. Discrimination was determined by the area under the receiver operating characteristic curve; calibration was assessed by the Hosmer and Lemeshow test and the Spiegelhalterz test. A total of 9449 bacterial strains were isolated in 6207 patients; 27.2% were <6 months old at the first episode. Enterobacteriales (Escherichia coli and other Enterobacteriales) accounted for 80.4% of all isolates. Amoxicillin-clavulanate (AMC) and cefixime (CFI) Enterobacteriales resistance was 32.8% and 13.7%, respectively, and remained quite stable among the different age groups. On the contrary, resistance to ciprofloxacin (CIP) (overall 9.6%) and cotrimoxazole (SXT) (overall 28%) increased with age. After multivariable analysis, resistance to AMC/CFI could be predicted by the following: sex; age at sampling; department of admission; previous number of bacterial pathogens isolated. Resistance to CIP/SXT could be predicted by the same factors, excluding sex. The models achieved very good calibration but moderate discrimination performance. Specific antibiotic resistance among Enterobacteriales could be predicted using the proposed scoring system to guide empirical antibiotic choice. Further studies are needed to validate this tool.

Background: Breast cancer is a well-recognised late adverse effect in female childhood cancer survivors (CCSs), especially after chest radiotherapy; information on subsequent male breast cancer (SMBC) is limited. We summarised the existing evidence on SMBC after childhood cancer in a systematic review and investigated the risk of SMBC among males in a Pan-European cohort., Methods: We searched Medline/PubMed for cohort studies and case reports/series that assessed SMBC after childhood cancer (≤21 years). Furthermore, we analysed data on SMBC in the PanCareSurFup cohort, reporting standardised incidence ratios (SIRs), absolute excess risks (AERs), and 5- and 10-year survival rates., Results: The systematic review included 38 of 7080 potentially eligible articles. Cohort-specific SMBC frequencies were 0-0.40% (31 studies). SMBC occurred after a follow-up ranging from 24.0 to 42.0 years. Nine case reports/series described 11 SMBC cases, occurring 11.0-42.5 years after primary childhood cancer. In the PanCareSurFup cohort (16 SMBC/37,738 males; 0.04%), we observed a 22.3-fold increased risk of SMBC relative to the general male population (95% CI 12.7-36.2; absolute excess risk/100,000 person-years: 2.3, 95% CI 1.3-3.7). The five- and ten-year survival rates after SMBC diagnosis were 60.3% (95% CI 35.6%-85.0%) and 43.0% (95% CI 16.1%-69.9%), respectively. Clear evidence of risk factors did not emerge from these comprehensive efforts., Conclusions: Compared to the general population, male CCSs have an elevated risk of developing subsequent breast cancer, although the absolute risk is low. Health care providers should be aware of this rare yet serious late effect; male CCSs with symptoms potentially related to SMBC warrant careful examination., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Late mortality of European 5-year survivors of childhood or adolescent cancer has dropped over the last 60 years, but excess mortality persists. There is little information concerning secular trends in cause-specific mortality among older European survivors. PanCareSurFup pooled data from 12 cancer registries and clinics in 11 European countries from 77 423 five-year survivors of cancer diagnosed before age 21 between 1940 and 2008 followed for an average age of 21 years and a total of 1.27 million person-years to determine their risk of death using cumulative mortality, standardized mortality ratios (SMR), absolute excess risks (AER), and multivariable proportional hazards regression analyses. At the end of follow-up 9166 survivors (11.8%) had died compared to 927 expected (SMR 9.89, 95% confidence interval [95% CI] 9.69-10.09), AER 6.47 per 1000 person-years, (95% CI 6.32-6.62). At 60 to 68 years of attained age all-cause mortality was still higher than expected (SMR = 2.41, 95% CI 1.90-3.02). Overall cumulative mortality at 25 years from diagnosis dropped from 18.4% (95% CI 16.5-20.4) to 7.3% (95% CI 6.7-8.0) over the observation period. Compared to the diagnosis period 1960 to 1969, the mortality hazard ratio declined for first neoplasms (P for trend <.0001) and for infections (P < .0001); declines in relative mortality from second neoplasms and cardiovascular causes were less pronounced (P = .1105 and P = .0829, respectively). PanCareSurFup is the largest study with the longest follow-up of late mortality among European childhood and adolescent cancer 5-year survivors, and documents significant mortality declines among European survivors into modern eras. However, continuing excess mortality highlights survivors' long-term care needs., (© 2021 UICC.)

Objectives: The area under a receiver operating characteristic (ROC) curve (AUC) is a popular measure of pure diagnostic accuracy that is independent from the proportion of diseased subjects in the analysed sample. However, its actual usefulness in the clinical context has been questioned, because it does not seem to be directly related to the actual performance of a diagnostic marker in identifying diseased and non-diseased subjects in real clinical settings. This study evaluates the relationship between the AUC and the proportion of correct classifications (global diagnostic accuracy, GDA) in relation to the shape of the corresponding ROC curves., Methods: We demonstrate that AUC represents an upward-biased measure of GDA at an optimal accuracy cut-off for balanced groups. The magnitude of bias depends on the shape of the ROC plot and on the proportion of diseased and non-diseased subjects. In proper curves, the bias is independent from the diseased/non-diseased ratio and can be easily estimated and removed. Moreover, a comparison between 2 partial AUCs can be replaced by a more powerful test for the corresponding whole AUCs., Results: Applications to 3 real datasets are provided: a marker for a hormone deficit in children, 2 tumour markers for malignant mesothelioma, and 2 gene expression profiles in ovarian cancer patients., Conclusions: The AUC is a measure of accuracy with potential clinical relevance for the evaluation of disease markers. The clinical meaning of ROC parameters should always be evaluated with an analysis of the shape of the corresponding ROC curve.

(1) Background: Intraoral scanners (IOS) are widely used in prosthodontics. However, a good trueness is mandatory to achieve optimal clinical results. The aim of the present in vitro study was to compare two IOS considering the operator's experience and different implant clinical scenarios. (2) Methods: Two IOS (IT-Itero, Align Technology; and OP-Opera MC, Opera System, Monaco) were compared simulating three different clinical scenarios: single implant, two implants, and full-arch rehabilitation. Ten scans were taken for each configuration by two different operators (one expert, one inexperienced); influence of operator experience and the type of scanner used was investigated. (3) Results: Trueness of the scans differed between the experienced and non-experienced operator and this difference was statistically significant in all the three scenarios ( p = 0.000-0.001, 0.037). A significant difference was present between the scanners ( p = 0.000), in the two-implant and full-arch scenarios ( p = 0.00). (4) Conclusions: Experience of the operator significantly affect trueness of IT and OP scanners. A statistically significant difference was present among IOS in the two-implant and full-arch scenarios.

Purpose: Long-term success of titanium dental implants is influenced by various factors, including the maintenance of good oral hygiene. The present study aimed to evaluate cleaning effectiveness and patient satisfaction with glycine powder air polishing and traditional professional oral hygiene treatments when applied to implant-supported full-arch restorations without removal of the fixed prosthesis., Materials and Methods: A total of 85 patients with 357 implants supporting full-arch fixed restorations were included. After removal of the prosthesis (T0), the following parameters were recorded: Plaque Index, peri-implant spontaneous bleeding, probing depth and bleeding on probing. The prosthesis was then reinserted. The patients were divided into three groups, each of which received two hygiene therapies randomly administered in each hemiarch using a split-mouth design. The possible treatments were glycine powder air polishing and use of sponge floss vs sponge floss only in group 1; glycine powder air polishing vs use of an ultrasonic device with a polyetheretherketone fibre tip coating in group 2; and glycine powder air polishing vs use of carbon fibre curettes and sponge floss in group 3. After instrumentation, the prostheses were removed to assess the Plaque Index and peri-implant spontaneous bleeding. Questionnaires were used to record patients' levels of comfort and satisfaction in relation to the various treatments., Results: Glycine powder air polishing resulted in a significantly higher reduction in plaque around implants compared to control treatments (sponge floss only, ultrasonic device with polyetheretherketone fibre tip coating, and manual scaling with carbon fibre curettes and use of sponge floss) (P = 0.020). Glycine powder air polishing followed by application of sponge floss provided the greatest reduction of plaque deposits on the prosthetic surfaces. On average, 80% of patients rated glycine powder air polishing highest with regard to satisfaction., Conclusions: Glycine powder air polishing is a highly effective and comfortable treatment to maintain good oral hygiene in clinical practice, and could be used as an alternative to manual and mechanical instrumentation when dealing with implant-supported restorations.

Background: Although full-arch immediately loaded rehabilitations are widely used nowadays, little information is available on which implant/abutment connection is the most suitable in this type of treatment., Purpose: The aim of the present multicentric split-mouth clinical trial was to compare the clinical outcomes of two different implant-abutment connections applied in full-arch immediate loading rehabilitations: external hexagon connection (EHC) versus internal hexagon connection (IHC)., Materials and Methods: Twenty patients were rehabilitated with immediately loaded fixed full-arch rehabilitations. All the implants presented the same macro- and micro-topography but different implant/abutment connection. IHC were used in one randomly selected side of the jaw and EHC in the other side. Outcome measures were implant survival rate, peri-implant marginal bone loss (MBL), plaque index (PI), probing depth (PD), and bleeding on probing (BoP) evaluated at 3, 6, 12, and 36-month post-loading. Any technical and biological complication was recorded. Kaplan-Meier procedure and linear mixed model were used to perform statistical analysis., Results: Forty-three EHC and 40 IHC implants were inserted. No patients dropped out and two implants failed in the first 6 months. The CSR was 97.7% for EHC and 97.5% for IHC implants. No statistically significant differences were found among the two groups for any of the parameters at any time point. At the 36-month follow-up visit a slight difference was found in MBL with a mean value of 1.7 mm in the EHC and of 1.9 mm in the IHC group (p = 0.355). No biologic complications were identified. Seven loosed abutment screws were identified in the entire follow-up period, two in the EHC, and five in the IHC group without a statistically significant difference (p = 0.394)., Conclusions: After 36 months in function, both internal and external hexagon connections provided good clinical outcomes and were not associated with any significant difference., (© 2021 The Authors. Clinical Implant Dentistry and Related Research Published by Wiley Periodicals LLC.)

The purpose of this systematic review was to investigate the clinical outcomes of frameworks made of different materials in patients with implant-supported full-arch prostheses. A literature search was conducted on MEDLINE, Scopus and Cochrane Library, until the 1st of March 2021, with the following search terms: framework or substructure combined with "dental implants". The outcomes evaluated were: implant and prosthesis survival, bone resorption, biological and technical complications. The Cochrane Handbook for Systematic Reviews of Interventions was employed to assess the risk of bias in randomized clinical trials. The Newcastle-Ottawa quality assessment scale was used for non-randomized studies. In total, 924 records were evaluated for title and abstract, and 11 studies were included in the review: 4 clinical randomized trials and 7 cohort studies. The framework materials investigated were: gold alloy, titanium, silver-palladium alloy, zirconia and polymers including acrylic resin and carbon-fiber-reinforced composites. High implant and prosthetic cumulative survival rates were recorded by all included studies. Various materials and different fabrication techniques are now available as alternatives to traditional cast metal frameworks, for full-arch implant-supported rehabilitations. Further long-term studies are needed to validate the use of these materials and clarify their specific clinical indications and manufacturing protocols to optimize their clinical outcomes.

Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium . Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs.

Oral squamous cell carcinoma (OSCC) is a widespread malignancy with high mortality. In particular, a delay in its diagnosis dramatically decreases the survival rate. The aim of this systematic review was to investigate and summarize clinical results in the literature, regarding the potential use of salivary microRNAs (miRNAs) as diagnostic and prognostic biomarkers for OSCC patients. Twelve papers were selected, including both case-control and cohort studies, and all of them detected significantly dysregulated miRNAs in OSCC patients compared to healthy controls. Based on our results, salivary miRNAs might provide a non-invasive and cost-effective method in the diagnosis of OSCC, and also to monitor more easily its evolution and therapeutic response and therefore aid in the establishment of specific therapeutic strategies.

Specific microRNA (miRNA) expression profiles have been reported to be predictive of specific clinical outcomes of dental implants and might be used as biomarkers in implant dentistry with diagnostic and prognostic purposes. The aim of the present narrative review was to summarize current knowledge regarding the use of miRNAs in implant dentistry. The authors attempted to identify all available evidence on the topic and critically appraise it in order to lay the foundation for the development of further research oriented towards the clinical application of miRNAs in implant dentistry., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide., Methods: The PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence., Results: 427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN-comparable to the risk among members of the general population with at least two first-degree relatives affected., Conclusions: Colonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken., Competing Interests: Competing interests: HL and TW are shareholders in, and have signed an intellectual property agreement with the company Concidera Health. The company develops clinical decision support tools for childhood cancer survivorship., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This pilot study was conducted to evaluate the cleaning efficacy of an angled implant brush for home oral hygiene of full-arch fixed-implant prostheses., Methods: Forty-one patients treated with a full-arch implant rehabilitation in the maxilla or mandible (164 implants) for at least 4 months were enrolled. The screw-retained fixed prostheses were removed and baseline (T0) parameters were recorded, including plaque index (PI), probing depth (PD), and bleeding on probing (BOP). All patients completed a 5-item questionnaire on hygiene maintenance and received an implant brush for home hygiene. After 1 month (T1) PI, PD, and BOP were recorded again and patients completed a 7-item questionnaire to evaluate their satisfaction with the implant brush. One-way repeated-measures analysis of variance was conducted to evaluate the significance of changes in PI, PD, and BOP. A P value <0.05 was considered to indicate statistical significance., Results: A statistically significant reduction of BOP (0.62±0.6 at T0 vs. 0.5±0.5 at T1; P =0.032) was found, while no statistically significant changes in PD (1.74±0.5 mm at T0 vs. 1.77±0.5 mm at T1; P =0.050) or PI (1.9±0.7 at T0 vs. 1.7±0.7 at T1; P =0.280) occurred. According to the 7-item questionnaire, patients reported no difficulty in using the angled brush (63.4%) and deemed it highly (46.3%) or very highly (4.8%) effective in improving their home oral hygiene., Conclusions: Within the limits of the present pilot study, the patients experienced a reduction of BOP 1 month after being instructed to use the angled implant brush. The angled implant brush appeared to be a well-accepted device for home-care hygiene of full-arch fixed-implant rehabilitations., Competing Interests: No potential conflicts of interest relevant to this article was reported., (Copyright © 2020. Korean Academy of Periodontology.)

Background: The etiology of peri-implantitis is multifactorial, and it is not directly linked to the quantitative amount of plaque. The aim of this study was to evaluate the influence of subgingival microbiota around implants supporting full-arch restorations on clinical indexes of peri-implant health., Method: 47 patients (54 full-arch fixed rehabilitations) were included. Based on the highest value of probing depth (PD), 47 implants (in the test arch), 40 natural teeth and 7 implants (in the antagonist arch) were selected for microbiological sampling (traditional PCR and real-time PCR). Periodontal indexes (plaque index, PlI; probing depth, PD; bleeding on probing, BOP; peri-implant suppuration, PS) and marginal bone loss were also recorded., Results: Despite abundant plaque accumulation, the peri-implant parameters were within normal limits. No statistical difference was found in the microbial population around the test implants and antagonist natural teeth. Treponema denticola was present in a significantly higher amount around implants with increased PlI. Implants with increased BOP showed a significant increase in Treponema denticola and Tannerella forsythia. A significantly higher presence of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia was identified around the implants affected by peri-implantitis and in smokers., Conclusions: Peri-implantitis is characterized by a complex and polymicrobial disease, that might be influenced by the qualitative profile of plaque. Smoking might also favor implant biological complications in full-arch fixed prosthesis.

Background: Ultraviolet (UV) and non-thermal plasma functionalization are surface treatment modalities that seem able to improve osseointegration. The aim of this systematic review and meta-analysis is to assess the effect of the two methods and possible differences., Materials and Methods: The systematic research of pre-clinical animal studies was conducted up to May 2020 in the databases PubMed/Medline, Scopus and the Cochrane Lybrary. A meta-analysis was performed by using the DerSimonian-Laird estimator in random-effects models., Results: Through the digital search, 518 articles were identified; after duplicate removal and screening process 10 papers were included. Four studies evaluating UV treatment in rabbits were included in the meta-analysis. The qualitative evaluation of the included studies showed that both UV photofunctionalization and non-thermal plasma argon functionalization of titanium implant surfaces might be effective in vivo to improve the osseointegration. The meta-analysis on four studies evaluating UV treatment in rabbits showed that bone to implant contact values (expressed as standardized mean differences and raw mean differences) were significantly increased in the bio-activated groups when follow-up times were relatively homogeneous, although a high heterogeneity ( I 2 > 75%) was found in all models., Conclusions: The present systematic review and meta-analysis on pre-clinical studies demonstrated that chair-side treatment of implants with UV or non-thermal plasma appear to be effective for improving osseointegration. This systematic review supports further clinical trials on this topic.

Objectives: The purpose of this study was to evaluate the primary stability of two implants with the same macro- and micromorphology but different thread design and analyze their clinical outcomes over a one-year period., Materials and Methods: 14 patients needing a partial rehabilitation with a delayed loading approach (DEL group: 9 patients) or a full-arch rehabilitation treated with immediately loaded fixed prostheses supported by 4 implants following the Columbus Bridge Protocol (CBP) (IL group: 5 patients) were included. In each patient, at least one SY (implant with standard threads) and one SL implant (implant with an augmented depth of the threads) were randomly inserted. Primary outcome measures were the number of threads exposed at a torque of 30 Ncm and 50 Ncm and final insertion torque. Secondary outcome measures were implant and prosthetic failure, peri-implant bone resorption, and periodontal parameters: bleeding on probing (BoP), plaque index (PI), and probing depth (PD) evaluated at 3, 6, and 12 months of healing., Results: Nineteen SY and 19 SL implants were inserted in 14 patients. Twenty implants (10 SL and 10 SY) were inserted in the IL group, while 18 (9 SL and 9 SY) were inserted in the DEL group and followed-up for 12 months. No patients dropped out. No implants and prostheses failed. No biological complications were identified. No significant differences were found between SY and SL implants comparing the number of exposed threads when inserting the implant with a torque insertion of 30 N ( T student test p = .142 and U test p = .164). At 50 N, no threads were visible in either groups. Final torque insertion values were higher for SL (mean: 48.42 Ncm) compared to SY implants (mean: 43.42 Ncm) without a statistically significant difference. All the implants showed good clinical outcomes at the 1-year-in-function visit., Conclusions: After 12 months of function, both implant types provided good clinical outcomes without statistically significant differences between the two groups. A difference in insertion torque (even if not statistically significant) was found with higher insertion torque values for SL implants with a larger thread depth., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Maria Menini et al.)

Background: To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC)., Methods: The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI., Results: A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI., Conclusions: We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies., Trial Registration: Clinicaltrials.gov NCT01399281; ENCePP seal: awarded on 25 November 2011.

Background: The onset of bronchiolitis obliterans (BO) as a pulmonary manifestation of chronic graft vs host disease dramatically changes the prognosis of children undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to evaluate the overall survival (OS) of children with BO treated with imatinib mesylate (IM)., Methods: This study included children who underwent allo-HSCTs between January 2000 and December 2016., Results: Among 345 patients who underwent HSCTs, 293 were evaluable for BO and 26 (8.9%) developed BO. The cumulative incidence of BO was 4.8% (95% confidence interval [CI], 2.8-7.5) at 1 year and 7.7% (95% CI, 5.1-11.1) at 3 years after transplantation. In the group of HSCTs (n = 67) complicated by chronic GvHD (c-GVHD), the incidence rate of BO was 38.8%. In total, 96.1% of patients with BO had c-GvHD worse than moderate grade, which was present in 70.7% of patients without BO (P = .011). The mortality rates were 46.1% in the BO group and 27.4% in the group without BO. Half of the patients with BO (n = 13) received IM, and the overall response rate was 76.9%. Four years after HSCT, OS was 42.6% (95% CI, 18.2-65.3) in the group without IM and 83.3% (95% CI, 27.3-97.5) in the group with IM., Conclusions: BO after HSCT in the pediatric population has a high incidence and mortality rate. In terms of overall response and tolerability, this study showed relevant improvements in the prognosis of children with BO after the introduction of IM. Further prospective studies among children are needed to confirm these results., (© 2020 Wiley Periodicals, Inc.)

The aim of the present report was to evaluate the clinical outcomes of edentulous jaws rehabilitated with the Brånemark Novum protocol over a 16-year period. Between April and November 2001, four patients (three males, one female) were rehabilitated with fixed full-arch rehabilitations supported by three immediately loaded implants following the Brånemark Novum protocol. Cumulative survival rates (CSRs) of the implants and prosthesis, bleeding on probing (BOP), Plaque Index (PI), probing depth (PD), implant stability quotient (ISQ; as measured through resonance frequency analysis [RFA]), and peri-implant bone resorption were evaluated over time, up to the 16-year follow-up. At 16 years of follow-up, no implant failed (CSR 100%) and no prosthesis needed to be substituted (CSR 100%). During the period between the 11th and 16th year of follow-up, bone level (mean: 2.2 mm at 16 years) and RFA values remained stable. At the 16-year follow-up, the implants presented high PI (79.2%) but low BOP (10.4%) values. Mean PD was 3.30 mm (range: 2 to 6 mm). One biologic complication was detected on a central implant (crater-form bone destruction), and several prosthodontic complications occurred during the 16 years (fractures of resin or teeth), the majority of which were registered on the same parafunctional patient. This is the first description of the Brånemark Novum protocol rehabilitation with a 16-year follow-up. The outcomes demonstrated very good long-term outcomes for this protocol.

Objective: To compare the long-term disease state, in terms of activity and damage, of children with juvenile idiopathic arthritis (JIA) who had their disease onset in methotrexate (MTX) or biologic eras., Methods: Patients were included in MTX or biologic era cohort depending on whether their disease presentation occurred before or after January 2000. All patients had disease duration ≥ 5 years and underwent a prospective cross-sectional assessment, which included measurement of disease activity and damage. Inactive disease (ID) and low disease activity (LDA) states were defined according to Wallace, JADAS10, and cJADAS10 criteria. Articular and extraarticular damage was assessed with the Juvenile Arthritis Damage Index (JADI)., Results: MTX and biologic era cohorts included 239 and 269 patients, respectively. Patients were divided in the "functional phenotypes" of oligoarthritis and polyarthritis. At cross-sectional visit, patients in the biologic era cohort with either oligoarthritis or polyarthritis had consistently higher frequencies of ID and LDA by all criteria. The measurement of disease damage at cross-sectional visit revealed that the frequency of impairment of > 1 JADI-Articular items was higher in MTX than in biologic era cohort (17.6% versus 11% in oligoarthritis and 52.6% versus 21.8% in polyarthritis). Likewise, frequency of involvement of > 1 JADI-Extraarticular items was higher in the MTX than in the biologic era cohort (26.5% versus 16.2% in oligoarthritis and 31.4% versus 13.5% in polyarthritis)., Conclusion: Our study provides evidence of the remarkable outcome improvement obtained with the recent therapeutic advance in JIA.

Objectives: To describe a single institution experience on echo-guided percutaneous bicaval double lumen extracorporeal membrane oxygenation cannulation performed at the bedside by intensivists., Design: Retrospective observational study., Setting: Extracorporeal membrane oxygenation team of a tertiary care children's hospital., Patients: All patients 0-14 years old undergoing venovenous extracorporeal membrane oxygenation from January 1, 2013, to January 1, 2018., Interventions: None., Measurements and Main Results: Thirty children underwent 32 extracorporeal membrane oxygenation runs. Median age at enrollment was 2 months (interquartile range, 0-20.5 mo), 65.6% of the runs (21 patients) were performed in newborns (n = 13, 40.6%) or infants (n = 8, 25%). Median preextracorporeal membrane oxygenation index was 66.9 (interquartile range, 50-85.6). Major comorbidities were present in 50% of patients. All patients were cannulated percutaneously. In two cases cannulation occurred from the left internal jugular vein. Extracorporeal membrane oxygenation was effective in increasing pH, arterial oxygen saturation, PaO2, and lowering PaCO2. The overall differences in pre and postextracorporeal membrane oxygenation values were statistically significant, while stratifying patients according to the cannula diameter (mm)/major diameter of the cannulated internal jugular vein (mm) ratio (> 0.67 or ≤ 0.67), statistical significance was reached only for the highest ratio. Complications were observed in three runs: two cannula tip dislocations in the right atrium and one limited flow in the only case in which an Avalon cannula was not used. In 20 cases (62.5% of 32 runs), the cannulated vessel was patent at follow-up or autopsy. A ratio less than or equal to 0.67 or greater than 0.67 did not influence the occurrence rate of complications, nonpatency of the internal jugular vein, death for intracranial bleeding and death at 30 days from extracorporeal membrane oxygenation discontinuation. Overall cumulative survival at 30 days from extracorporeal membrane oxygenation discontinuation was 60% (95% CI, 40-75), with a survival advantage in the case of ratio greater than 0.67 (65%; 95% CI, 44-80 vs 25%; 95% CI, 0-60)., Conclusions: The described technique proved to be feasible, safe, and effective. Further investigation is needed.

Objective: To seek predictors of therapeutic response to the interleukin (IL)-1 inhibitor anakinra in children with systemic-onset juvenile idiopathic arthritis (sJIA)., Methods: The clinical charts of all patients with sJIA who were newly treated with anakinra at our center between 2004 and 2017 were reviewed retrospectively. Predictors included baseline demographic, clinical, and laboratory variables as well as previous or concomitant therapies. The effectiveness of anakinra was assessed at 1 year after treatment start. Complete clinical response (CCR) was defined as absence of fever, physician's global assessment ≤ 1, count of active joints ≤ 1, negative C-reactive protein, and ≥ 75% reduction of corticosteroid dose. According to the intention-to-treat principle, patients who had anakinra discontinued before 1 year for any reasons other than disease remission were classified as nonresponders. Statistics included univariate and multivariable analyses., Results: Of the 62 patients included in the study, 24 (39%) met the criteria for CCR at 1 year, whereas 38 (61%) did not. On multivariable analysis, independent correlations with achievement of CCR were identified for shorter disease duration, lower active joint count, higher ferritin level, and greater activity of systemic manifestations. The area under the curve of the model was 0.83., Conclusion: Our findings help to delineate the clinical profile of patients with sJIA who are more likely to benefit from IL-1 blockade. They also underscore the need for studies aimed at examining the therapeutic role of early IL-1 inhibition and to identify biomarkers predicting response to either IL-1 or IL-6 antagonists.

Background: Scientific literature shows a high prevalence of Small Intestinal Bacterial Overgrowth (SIBO) in patients with Cystic Fibrosis (CF). The role of SIBO in nutritional status and gastrointestinal symptoms in CF is not known. Our aim was to study epidemiology and clinical impact of SIBO while assessing the efficacy of rifaximin in eradicating SIBO in CF patients., Methods: Symptoms questionnaire and Glucose Breath Test (GBT) were given to 79 CF patients (median age 19.6 years; 9.2-36.9). Subjects with a positive GBT were enrolled in a randomized controlled trial and received rifaximin 1200 mg for 14 days or no treatment. Questionnaire and GBT were repeated 1 month after the end of treatment or 45 days after the first negative GBT., Results: Out of 79 patients, 25 were affected by SIBO (31.6%) with a significant correlation with lower BMI, SDS-BMI (p < 0.05) and serum albumin levels (p < 0.05), independently from pancreas insufficiency. Twenty-three patients took part in the randomized trial, 13 patients (56.5%) in rifaximin group and 10 patients (43.5%) in control group. Eradication rate of SIBO was 9/10 (90%) in rifaximin group and 2/6 (33.3%) in control group (p < 0.05). In the rifaximin group, gastrointestinal symptom improvement was observed in 4/5 patients aged ≤ 14 years and in 0/5 patients aged > 14 years (p < 0.05); in 2/6 patients in the control group., Conclusions: CF patients show a high prevalence of SIBO, related to a poorer nutritional status. Rifaximin therapy is well tolerated and the results are promising in terms of efficacy in eradicating small intestinal bacterial overgrowth in CF.

Introduction: Advances in paediatric oncology led to the increase in long-term survival, revealing the burden of therapy-related long-term side effects. We evaluated overall and cause-specific mortality in a large cohort of Italian childhood cancer survivors (CCSs) and adolescent cancer survivors identified through the off-therapy registry., Materials and Methods: CCSs alive 5 years after cancer diagnosis occurring between 1960 and 1999 were eligible; the last follow-up was between 2011 and 2014. Outcomes were reported as standardised mortality ratios (SMRs) and absolute excess risks (AERs)., Results: Among 12,214 CCSs, 1113 (9.1%) deaths occurred. Survival at 35 years since diagnosis was 87% (95% confidence interval [CI]: 86-88) and at 45 years was 81% (95% CI: 77-84). CCSs had an 11-fold increased risk of death (SMR 95% CI: 10.7-12), corresponding to an AER of 48 (95% CI: 45-51). Mortality decreased by 60% for survivors treated most recently (1990-1999). The most frequent causes of death were recurrence of the original cancer (56%), a subsequent neoplasm (19%) and cardiovascular diseases (5.8%). Among those who survived at least 15 years after diagnosis, a secondary malignancy was the leading cause of death., Conclusions: This study confirms the impact of recent advances in anticancer therapy in reducing mortality, mainly attributable to recurrence but also to other causes. However, overall mortality continues to be higher than in the general population. A long-term follow-up is needed to prevent late mortality due to secondary neoplasms and non-neoplastic causes in CCSs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)