Relatie tussen mesiodens en standafwijkingen, diastemen en eruptiestoornissen van frontelementen

Een mesiodens wordt vaak bij toeval tijdens een röntgenonderzoek ontdekt. Soms wordt een mesiodens röntgenologisch gediagnosticeerd bij een klinisch waargenomen centraal diasteem en een eruptiestoornis of een rotatie van een centrale incisief. In een retrospectief onderzoek is bij een groep van 162 jongeren in de leeftijd van 4 tot 18 jaar met een mesiodens nagegaan welke de frequenties van standafwijkingen, diastemen en eruptiestoornissen van frontelementen in de bovenkaak waren. Bij 72% van deze groep werden 1 of meer van deze afwijkingen geconstateerd. Verwijdering van een mesiodens bij jonge kinderen leidt meestal tot spontaan herstel van de afwijkingen. Vroege diagnostiek en behandeling zijn daarom belangrijk

Ongewenste neveneffecten van lokale anesthesie

Lokale anesthetica worden in de tandheelkunde frequent toegepast. Aangezien weinig gegevens bekend zijn over de incidentie van complicaties na toediening van lokale anesthesie, werd een prospectief onderzoek verricht onder een groep van 219 patiënten. Complicaties die het meest frequent werden waargenomen waren insufficiënte anesthesie (17%) en positieve aspiratie (3%). Pijn tijdens injecteren, parese van de nervus facialis, lokale bleekheid (´blanching´), hematoom en vasovagale collaps werden als afzonderlijke complicatie bij minder dan 1% van de patiënten waargenomen. De resultaten suggereerden dat toediening van een lokaal anestheticum geassocieerd is met een kleine kans op ongewenste neveneffecten en dat deze ongewenste neveneffecten meestal lokale complicaties betreffen met een beperkte omvang en ernst

Prognostic value of serial N-terminal pro-B-type natriuretic peptide measurements in adults with congenital heart disease

Background--A single NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurement is a strong prognostic factor in adult congenital heart disease. This study investigates NT-proBNP profiles within patients with adult congenital heart disease and relates these to cardiovascular events. Methods and Results--In this prospective cohort, 602 patients with adult congenital heart disease were enrolled at the outpatient clinic (years 2011-2013). NT-proBNP was measured at study inclusion in 595 patients (median age 33 [IQR 25-41] years, 58% male, 90% NYHA I) and at subsequent annual visits. The primary end point was defined as death, heart failure, hospitalization, arrhythmia, thromboembolic event, or cardiac intervention; the secondary end point as death or heart failure. Repeated measurements were analyzed using linear mixed models and joint models. During a median follow-up of 4.4 [IQR 3.8-4.8] years, a total of 2424 repeated measurements were collected. Average NT-proBNP increase was 2.9 pmol/L the year before the primary end point (n=199, 34%) and 18.2 pmol/L before the secondary end point (n=58, 10%), compared with 0.3 pmol/L in patients who remained end point-free (P-value for difference in slope 0.006 and < 0.

Round Spermatid Injection Rescues Female Lethality of a Paternally Inherited Xist Deletion in Mouse

In mouse female preimplantation embryos, the paternal X chromosome (Xp) is silenced by imprinted X chromosome inactivation (iXCI). This requires production of the noncoding Xist RNA in cis, from the Xp. The Xist locus on the maternally inherited X chromosome (Xm) is refractory to activation due to the presence of an imprint. Paternal inheritance of an Xist deletion (XpΔXist) is embryonic lethal to female embryos, due to iXCI abolishment. Here, we circumvented the histone-to-protamine and protamine-to-histone transitions of the paternal genome, by fertilization of oocytes via injection of round spermatids (ROSI). This did not affect initiation of XCI in wild type female embryos. Surprisingly, ROSI using ΔXist round spermatids allowed survival of female embryos. This was accompanied by activation of the intact maternal Xist gene, initiated with delayed kinetics, around the morula stage, resulting in Xm silencing. Maternal Xist gene activation was not observed in ROSI-derived males. In addition, no Xist expression was detected in male and female morulas that developed from oocytes fertilized with mature ΔXist sperm. Finally, the expression of the X-encoded XCI-activator RNF12 was enhanced in both male (wild type) and female (wild type as well as XpΔXist) ROSI derived embryos, compared to in vivo fertilized embryos. Thus, high RNF12 levels may contribute to the specific activation of maternal Xist in XpΔXist female ROSI embryos, but upregulation of additional Xp derived factors and/or the specific epigenetic constitution of the round spermatid-derived Xp are expected to be more critical. These results illustrate the profound impact of a dysregulated paternal epigenome on embryo d

Nivolumab in pre-treated malignant pleural mesothelioma: real-world data from the Dutch expanded access program

Background: Randomized phase III trials are ongoing to investigate the efficacy of nivolumab in malignant pleural mesothelioma (MPM), but real-world data are still scarce. In this real-world study, we investigated the clinical outcomes of nivolumab treatment in pre-treated MPM patients.Methods: Data from 107 nivolumab treated MPM patients within the Dutch expanded access program were retrospectively analyzed. Treatment was independent of programmed death ligand 1 (PD-L1) expression on tumor samples. Univariable and multivariable analyses were performed to evaluate the relationship between clinically important factors, baseline peripheral blood parameters and survival. The landmark method was used to compare the outcome of patients according to their radiological response.Results: In the full cohort, the median progression-free survival (mPFS) was 2.3 months (95% CI: 1.6-2.9) and the median overall survival (mOS) was 6.7 months (95% CI: 6.2-10.0). After 12 weeks, the disease control rate (DCR) was 37% and the objective response rate (ORR) was 10%. PD-L1 status was determined in 33 patients (30%) and PD-L1 positivity (>= 1%) was associated with an improved ORR (36% vs. 9%, P value 0.05), but not with PFS or OS. Low albumin was associated with worse OS (P value 0.002). Median OS was significantly longer for patients who had partial response to treatment (P value 0.0002).Conclusions: In this real-world analysis, ORR and mOS were lower compared to those obtained in phase II trials. However, exceptional survival rates were observed in patients who had a radiological response. Although we cannot determine whether prognostic or predictive, PD-L1 expression and albumin were associated with greater response rate and may represent useful biomarkers for nivolumab treatment in MPM.Pathogenesis and treatment of chronic pulmonary disease