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Treatment with CD19-directed (CAR) T cells has evolved as a standard of care for multiply relapsed or refractory large B-cell lymphoma (r/r LBCL). A common side effect of this treatment is the immune effector cell–associated neurotoxicity syndrome (ICANS). Severe ICANS can occur in up to 30% to 40% of patients treated with axicabtagene-ciloleucel (axi-cel), usually within the first 4 weeks after administration of the dose and usually responding well to steroids. We describe a case of progressive central neurotoxicity occurring 9 months after axi-cel infusion in a patient with r/r LBCL who had undergone a prior allogeneic hematopoietic cell transplant. Despite extensive systemic and intrathecal immunosuppression, neurological deterioration was inexorable and eventually fatal within 5 months. High CAR T-cell DNA copy numbers and elevated levels of interleukin-1 (IL-1) and IL-6 were found in the cerebral spinal fluid as clinical symptoms emerged, and CAR T-cell brain infiltration was observed on autopsy, suggesting that CAR T cells played a major pathogenetic role. This case of unexpected, devastating, late neurotoxicity warrants intensified investigation of neurological off-target effects of CD19-directed CAR T cells and highlights the need for continuous monitoring for late toxicities in this vulnerable patient population.

The circulating low-density lipoprotein concentration in blood can be reduced by the administration of statins. Frequently simvastatin (SV) is prescribed. Due to the reported pleiotropic effects of SV the aim of this study was to evaluate mineralization effects on human adipose tissue-derived stromal cells upon administration of SV. After informed consent human adipose tissue-derived stromal cells were obtained from tissue surplus of regular treatments of 14 individuals. According to established protocols after adding various SV concentrations (0.01 µM, 0.1 µM, 1.0 µM, 2.0 µM), alkaline phosphate (osteoblastic marker), mineralization capability and viability were determined at day 18, 21 and 28. The Kruskal–Wallis test was performed for statistical analysis. After adding SV a dose-dependent significant decreased viability and levels of alkaline phosphatase ( p < 0.01) and a significantly increased mineralization ( p < 0.01) of the primary cultures was recognized during the late mineralization stage. Mineralization of the human adipose tissue-derived stromal cells was induced by SV, possibly originated from alternative pathways than the alkaline phosphatase pathway. Further investigations should be performed regarding switching into the osteoblastic differentiation and as a possible source of cells that can be used as the basis for a potential bone graft substitute, which may allow an extension of the field of application.

Background: Alteration in kidney perfusion is an early marker of renal damage. The purpose of this study was to evaluate if changes in renal blood flow (RBF) could be detected using MRI with arterial spin labeling (ASL) technique. Methods: RBF as assessed by cortical (CRBF), medullary, and total renal blood flow (TRBF) were measured by MRI with arterial spin labeling (ASL-MRI) using flow-sensitive alternating inversion recovery true fast imaging with steady-state precession sequence. In 11 normotensive healthy individuals (NT) and 11 hypertensive patients (HT), RBF was measured at baseline and after both feet were covered with cold ice packs (cold pressor test) that activates the sympathetic nervous system. In another experiment, RBF was measured in 10 patients with CKD before and after a pharmacological intervention. We compared RBF measurements between the 3 study populations. Results: A significant reduction in CRBF (p = 0.042) and a trend in TRBF (p = 0.053) were observed in response to the activation of the sympathetic nervous system. A trend toward reduction of CRBF (p = 0.051) and TRBF (p = 0.059) has been detected after pharmacological intervention. TRBF was significantly lower in patients with HT and CKD patients compared to NT individuals (NT vs. HT, p = 0.014; NT vs. CKD, p = 0.004). TRBF was lower in patients with CKD compared to HT (p = 0.047). Conclusion: Our data indicate that both acute and short-term changes in RBF could be detected using ASL-MRI. We were able to detect differences in RBF between healthy and diseased individuals by needing only small sample size per group. Thus, ASL-MRI offers an advantage in conducting clinical trials compared to other technologies.

Although CD19-directed chimeric antigen receptor (CAR) T cells have been successfully used after a preceding allogeneic stem cell transplant (alloHCT) in patients with acute lymphoblastic leukemia, little is known about the feasibility and outcome of CAR T cell treatment in patients who have been previously allotransplanted for lymphoma. In a single-center retrospective analysis, course and outcome of all allografted patients treated with CD19 CAR constructs for B cell lymphoma between October 2018 and November 2019 were studied. CAR therapy consisted either of a third-generation CAR (HD-CAR-1) or of commercially manufactured axicabtagene ciloleucel (axi-cel; Gilead, Santa Monica, U.S.). Altogether, 10 CAR T cell dosings using recipient leukapheresis products were performed in 8 patients: 4 patients (2 mantle cell lymphoma, 2 chronic lymphocytic leukemia) received 6 dosings with HD-CAR-1 and 4 patients (all with diffuse large B cell lymphoma) received 4 dosings with axi-cel. Overall, 6 of 8 patients (75%) responded. CAR treatment was well tolerated with grade ≥ 3 cytokine release syndrome and neurotoxicity each being observed after 1 of 10 dosings. A single patient had moderate chronic graft-versus-host disease. Of note, 3 of 4 patients who received axi-cel had ongoing grade ≥ 3 cytopenia 3 months postdosing, whereas prolonged cytopenia was not observed in 9 alloHCT-naive patients who received axi-cel during the same time period. In conclusion, CAR T cell treatment from recipient-derived leukapheresis products after a prior alloHCT appears to be feasible, effective, and safe in patients with B cell lymphoma. Protracted cytopenia after axi-cel treatment is a matter of concern and requires further exploration.

Spectral-domain optical coherence tomography (SD-OCT) represents a reliable tool for retinal layer volume and thickness measurement. The aim of this study was to evaluate retinal changes indicating neurodegenerative processes in patients with end-stage renal disease (ESRD) compared to healthy controls. This was a cross-sectional, single-center study comprising 32 ESRD patients and 38 controls. Sectoral retinal nerve fiber layer (RNFL) thickness and retinal layer volumes were obtained by SD-OCT. Age- and gender-adjusted retinal layer volumes such as total retinal volume (p = 0.037), ganglion cell layer volume (GCL, p = 0.003), ganglion cell layer – inner plexiform layer volume (GCL-IPL, p = 0.005) and inner retinal layer volume (IRL, p = 0.042) of the right eye were lower in ESRD patients. Inner plexiform layer volume of both eyes (IPL, right eye: p = 0.017; left eye: 0.044) was reduced, as was RNFL thickness in the temporal superior sector (right eye: p = 0.016). A subgroup analysis excluding patients with diabetes revealed that GCL (p = 0.014) and GCL-IPL volume of the right eye (p = 0.024) and temporal superior sector of the RNFL scan (p = 0.021) in ESRD patients were still significantly thinner. We observed a decrease in several retinal layer volumes and temporal RNFL thickness indicative of retinal neurodegenerative processes in patients with ESRD.

Bone regeneration after oral and maxillofacial surgery is a long-term process, which involves various mechanisms. Recently, cold atmospheric plasma (CAP) has become known to accelerate wound healing and have an antimicrobial effect. Since the use of CAP in dentistry is not yet established, the aim of the present study was to investigate the effect of CAP on human calvaria osteoblasts (HCO). HCO were treated with CAP for different durations of time and distances to the cells. Cell proliferation was determined by MTT assay and cell toxicity by LDH assay. Additionally, RT-qPCR was used to investigate effects on osteogenic markers, such as alkaline phosphatase (ALP), bone morphogenic protein (BMP)2, collagen (COL)1A1, osteonectin (SPARC), osteoprotegerin (OPG), osterix (OSX), receptor activator of NF-κB (RANK), RANK Ligand (RANKL), and Runt-related transcription factor (RUNX)2. There were small differences in cell proliferation and LDH release regarding treatment duration and distance to the cells. However, an increase in the expression of RANK and RANKL was observed at longer treatment times. Additionally, CAP caused a significant increase in mRNA expression of genes relevant to osteogenesis. In conclusion, CAP has a stimulating effect on osteoblasts and may thus represent a potential therapeutic approach in the regeneration of hard tissue defects.

Aims Preserved vascular function represents a key prognostic factor in type 2 diabetes mellitus (T2DM), but data on vascular parameters in this patient cohort are scarce. Patients with T2DM often need more than one drug to achieve optimal glucose control. The aim of this study was to analyse the efficacy of two combination therapies on vascular function in subjects with T2DM. Methods and results This prospective, randomized study included 97 subjects with T2DM. Subjects were randomized to either the combination therapy empagliflozin (E) 10 mg with linagliptin (L) 5 mg once daily or metformin (M) 850 or 1000 mg twice daily with insulin glargine (I) once daily. At baseline and after 12 weeks, subjects had peripheral office and 24-h ambulatory blood pressure (BP) measurement and underwent vascular assessment by pulse wave analysis under office and ambulatory conditions. Office, 24-h ambulatory and central BP as well as pulse pressure (PP) decreased after 12 weeks of treatment with E + L, whereas no change was observed in M + I. There were greater decreases in 24-h ambulatory peripheral systolic (between-group difference: −5.2 ± 1.5 mmHg, P = 0.004), diastolic BP (−1.9 ± 1.0 mmHg, P = 0.036), and PP (−3.3 ± 1.0 mmHg, P = 0.007) in E + L than M + I. Central office systolic BP (−5.56 ± 1.9 mmHg, P = 0.009), forward pressure height of the pulse wave (−2.0 ± 0.9 mmHg, P = 0.028), 24-h ambulatory central systolic (−3.6 ± 1.4 mmHg, P = 0.045), diastolic BP (−1.95 ± 1.1 mmHg, P = 0.041), and 24-h pulse wave velocity (−0.14 ± 0.05m/s, P = 0.043) were reduced to a greater extent with E + L. Conclusion Beyond the effects on glycaemic control, the combination therapy of E + L significantly improved central BP and vascular function compared with the classic combination of M + I. ClinicalTrials.gov NCT02752113.

OBJECTIVE Initiation of antihypertensive drug treatment in low-risk individuals with grade 1 hypertension is under debate. The aim of this study was to examine the impact of mildly elevated blood pressure (BP) on early neurodegenerative processes independent of ageing. METHODS Sixty-two individuals were included in this study: 25 young (aged

Gingivafibroblasts were cultured on lithium disilicate, on zirconia dioxide, and on titanium with two different surface roughnesses (0.2 µm and 0.07 µm), Proliferation (MTT), Living/Dead staining, cytotoxicity (LDH), proliferation (FGF2), and inflammation (TNFα) were analyzed after 1 day and 21 days. Furthermore, alteration in cell morphology (SEM) was analyzed. The statistical analysis was performed by a Kruskal–Wallis test. The level of significance was set at p &lt, 0.05. There were no distinct differences in cellular behavior between the tested roughness. There were slight differences between tested materials. Cells grown on zirconia dioxide showed higher cytotoxic effects. Cells grown on lithium disilicate showed less expression of TNFα compared to those grown on zirconia dioxide or titanium. These effects persisted only during the first time span. The results indicate that the two tested high-strength ceramics and surface properties are biologically suitable for transmucosal implant components. The findings may help clinicians to choose the most appropriate biomaterial as well as the most appropriate surface treatment to use in accordance with specific clinical dental applications.

Objectives: About four million people are affected by rare diseases in Germany and 30 million in the EU. In 2013, a national action plan for people with rare diseases was adopted in Germany which is also aimed at improving the information situation and better gathering of information for affected patients and their families. Since then, various sources of information and medical care structures have been made available. The aim of this study was to evaluate the state of knowledge about information sources and health care centres for rare diseases among those affected. Methods: The study was carried out as anonymous survey among the member associations of the German Alliance for Chronic Rare Diseases (German acronym ACHSE e. V.). For this, a questionnaire was developed which in addition to questions on gender, age and disease comprised free text input referring to knowledge of health care centres or expert centres and source of information on rare diseases in Germany. Results: A total of 484 individuals suffering from 96 different rare diseases participated in the survey. Of these, 74.47% are aware of medical or dental care centres for treatment of their types of rare disease; 69.31% use self-help groups as a source of information, only a few respondents know government-sponsored "se-atlas" and "Orphanet". Conclusion: The majority of the respondents know medical care centres, most participants use self-help groups as information source, however, government-supported portals are largely unknown so that there is a need for further information in this regard.

Purpose: To investigate 2 generations of balloon-expandable covered stents as potential bridging devices using an in vitro model of stent-graft fenestrations. Materials and Methods: Twenty BeGraft and 20 BeGraft+ cobalt-chromium stents covered in expanded polytetrafluoroethylene (ePTFE) in 6- and 8-mm diameters were tested in sheets mimicking stent-graft fenestrations. Microscopy and radiography were employed to evaluate stent morphology after flaring. In vitro bench tests measured maximum pullout (perpendicular displacement) and the shear stress (axial displacement) forces needed to dislocate the stents. Results: No alteration of ePTFE coverage was detected in the flared stents. Digital radiography and computed tomography showed marked alteration of the stent geometry, which was more pronounced in the BeGraft group. No fractures were detected. Median (minimum–maximum) pullout forces for the 6-mm stent-grafts were 17.1 N (15.8–19.6) for the BeGraft device and 30.4 N (20.2–31.9) for the BeGraft+ device (p=0.006). Median (minimum–maximum) pullout forces for the 8-mm stent-grafts were 11.3 N (11–12.1) for the BeGraft device and 21.8 N (18.2–25.5) for the BeGraft+ device (p

BACKGROUND Flow-mediated vasodilatation (FMD) has become one of the most widely assessed parameters to analyse endothelial and vascular function in cardiovascular medicine. The degree of contribution of nitric oxide (NO) to FMD is inconclusive and varies widely depending on the device used. In this study, we used a semi-automatic ultrasound device to analyse to what extent basal NO activity contributes to FMD of the brachial artery. METHODS FMD was assessed with the UNEX EF device in a cross-over single blinded randomized study at baseline and then during infusion of either a NO-synthase-inhibitor (NG-monomethyl-L-arginine (L-NMMA)) or saline. The analysis was repeated after 1 week with the alternative infusion of L-NMMA or saline. All measurements were analysed both automatically and by a technician manually. RESULTS In total, 25 healthy men subjects completed the study. Diastolic blood pressure and heart rate significantly changed during infusion of L-NMMA. Infusion of L-NMMA reduced FMD significantly (-37%, p = 0.002). Saline solution had no effect on FMD (+14%, p = 0.392). Change in FMD was significantly different between the groups (ΔFMDL-NMMA vs. ΔFMDsaline , p = 0.032). There was a statistically significant correlation between automatically analysed results and those obtained by an experienced technician (FMDsaline : r = 0.822, p

Background Prospective studies describe a linkage between increased sodium intake and higher incidence of cardiovascular organ damage and end points. We analyzed whether tissue sodium content in the skin and muscles correlate with vascular hypertrophic remodeling, a risk factor for cardiovascular disease. Methods In patients with type 2 diabetes we assessed tissue sodium content and vascular structural parameters of the retinal arterioles. The structural parameters of retinal arterioles assessed by Scanning Laser Doppler Flowmetry were vessel (VD) and lumen diameter (LD), wall thickness (WT), wall-to-lumen ratio (WLR) and wall cross sectional area (WCSA). Tissue sodium content was measured with a 3.0 T clinical 23Sodium-Magnetic Resonance Imaging (23Na-MRI) system. Results In patients with type 2 diabetes (N = 52) we observed a significant correlation between muscle sodium content and VD (p = 0.005), WT (p = 0.003), WCSA (p = 0.002) and WLR (p = 0.013). With respect to skin sodium content a significant correlation has been found with VD (p = 0.042), WT (p = 0.023) and WCSA (p = 0.019). Further analysis demonstrated that tissue sodium content of skin and muscle is a significant determinant of hypertrophic vascular remodeling independent of age, gender, diuretic use and 24-hour ambulatory BP. Conclusion With the 23Na-MRI technology we could demonstrate that high tissue sodium content is independently linked to hypertrophic vascular remodeling in type 2 diabetes. Trial registration Trial registration number: NCT02383238 Date of registration: March 9, 2015.

Aims Impairment of vascular function contributes to the progression of chronic heart failure (HF) by increasing the afterload. Treatment with selective sodium‐glucose cotransporter 2 (SGLT2) inhibitors improves the prognosis of HF, but the precise mechanisms remain unclear. The aim of this study was to analyse the effect of empagliflozin on vascular function in patients with HF. Methods and results In an investigator initiated, double‐blind, randomized, placebo‐controlled, parallel‐group, clinical study, patients with HF NYHA II‐III and an ejection fraction of 49% or less were randomized 2:1 to receive empagliflozin 10 mg once daily or placebo for 3 months. A total of 74 patients (15% female), aged 66 ± 9 years, with a mean ejection fraction of 39 ± 8% and a median NTproBNP of 558 pg/mL (IQR 219–1051 pg/mL), were included. Vascular parameters such as central systolic blood pressure (cSBP), central pulse pressure (cPP), forward (FPH), and reflected pressure pulse height (RPH) decreased under resting conditions after 1 and 3 months (1 month: cSBP −6.4 ± 8.3 mmHg, P

Aims Analysis of microvascular parameters in the retinal circulation—known to reflect those in the systemic circulation—allows us to differentiate between eutrophic and hypertrophic remodelling of small arteries. This study aimed to examine microvascular changes in patients with congestive heart failure (CHF) and reduced as well as mid‐range ejection fraction. Methods and results Forty subjects with CHF underwent measurement of retinal capillary flow (RCF), wall‐to‐lumen ratio (WLR), vessel and lumen diameter, wall thickness, and wall cross‐sectional area (WCSA) of retinal arterioles of the right eye by scanning laser Doppler flowmetry (SLDF). Applying a matched pair approach, we compared this group with reference values of age‐matched controls from a random sample in the population of Pilsen, Czech Republic. There was no significant difference in RCF and WLR between the groups (RCF: P = 0.513; WLR: P = 0.106). In contrast, wall thickness and WCSA, indicators of hypertrophic remodelling, were higher in CHF subjects (WT: 15.0 ± 4.2 vs. 12.7 ± 4.2 μm, P = 0.021; WCSA: 4437.6 ± 1314.5 vs. 3615.9 ± 1567.8 μm2, P = 0.014). Similarly, vessel (109.4 ± 11.1 vs. 100.5 ± 14.4 μm, P = 0.002) and lumen diameter (79.0 ± 7.9 vs. 75.2 ± 8.5 μm, P = 0.009) were increased in CHF. Conclusions In CHF subjects, we observed hypertrophic remodelling of retinal arterioles indicative of similar changes of small resistance arteries in the systemic circulation. Microvascular structure and function assessed by SLDF may thereby represent a useful, non‐invasive method for monitoring of microvascular damage in patients with CHF and may offer innovative treatment targets for new CHF therapies.

Immunosuppressed patients like patients with leukemia or lymphoma, but also patients after autologous or allogeneic stem cell transplantation are at particular risk for an infection with COVID‐19. We describe a COVID‐19 outbreak on our leukemia and stem cell transplantation unit (LSCT‐Unit) originating from a patient with newly diagnosed acute myeloid leukemia. The patient was treated with intensive induction chemotherapy and we characterize the subsequent outbreak of COVID‐19 on a LSCT‐Unit. We describe the characteristics of the 36 contacts among the medical team, the results of their PCR and antibody tests and clinical aspects and features of infected employees. Of these 36 close contacts, 9 employees of the LSCT‐Unit were infected and were tested positive by PCR and/or antibody‐testing. 8/9 of them were symptomatic, 3/9 with severe, 5/9 with mild symptoms, and one person without symptoms. Due to stringent hygiene measures, the outbreak did not lead to infections of other patients despite ongoing clinical work. Moreover, we demonstrate that incubation period and clinical course of a COVID‐19 infection in an immunosuppressed patient could be unusual compared to that of immunocompetent patients. Consistent PCR and antibody testing are helpful to understand, control, and prevent outbreaks. For the safety of health‐care workers and patients alike, all employees wore FFP2 masks and were trained to adhere to several further safety guidelines. The implementation of rigorous hygiene measures is the key to controlling an outbreak and preventing infections of other patients.

Hemifacial microsomia (HFM) is also known as malformation of the first and second branchial arches (BAs), oculoauriculovertebral dysplasia syndrome, and Goldenhar syndrome. Possibilities resulting from CAD/CAM may be a valuable tool to existing procedures to treat these abnormalities. The aim of this study was to report a case where the planning and implementation of an intraorally inserted 2-part patient-specific mandible implant was used for the treatment of HFM esthetic remained problem after orthognathic surgery. A 20-year-old female patient who continued to suffer from the esthetic defect of the unilateral hypoplastic mandible after completion of the orthognathic surgery attended for consultation. Using CT scan and the software Geomagic Freeform (3D Systems, USA), a 2-piece titanium implant was designed and printed to restore the osseous frame of the basal border of the mandible. The base was made of solid polished titanium to minimize soft tissue abrasion. Due to its split design, the implant could be placed anatomically exactly at the mandibular margin via an intraoral access and to avoid damage of the mental nerve. There were no postoperative complications such as infections, soft tissue reactions to the implant, sensitivity disorders, or dehiscence. The occlusion was regular. A measurement of the postoperative x-rays showed a clear increase in bony symmetry. No postoperative pain or trismus was seen. Functionally, the therapy ended with the completion of wound healing and the jaw was fully resilient again. A combined treatment using PSI and additional autogenous fat grafting may represent a valid treatment option for the treatment of facial asymmetry in patients with HFM.

(1) Background: The aim of the study was to investigate the oral health&ndash, related quality of life (OHRQoL) of patients with oral lichen planus (OLP) and to evaluate differences between the various clinical forms of OLP. Specifically, the differences in OHRQoL, physical pain levels and eating restriction were assessed, (2) Methods: One hundred and twelve patients with clinical and histological features of OLP from the Department of Cranio-Maxillofacial Surgery of the M&uuml, nster University Hospital participated in this prospective study. OHRQoL was analysed by using the German short version of the Oral Health Impact Profile (OHIP-14). Physical pain levels and restriction in eating were rated on visual analogue scales (VAS). The statistical analysis was performed using the Mann&ndash, Whitney U-Test and the chi-squared test with a significance level at p = 0.05, (3) Results: Group 1 consisted of patients with reticular OLP (n = 50) and group 2 of patients with atrophic, erosive-ulcerative or bullous OLP (n = 62). The average OHIP-14 score was 13.54 points and differed significantly between the two groups. There were significant differences in the domains &ldquo, physical pain&rdquo, &ldquo, psychological discomfort&rdquo, physical disability&rdquo, and &ldquo, social disability&rdquo, The VAS &ldquo, score and &ldquo, restriction in eating&rdquo, score varied significantly between the clinical forms. Positive correlations were found between the OHIP-14 total scores and the VAS scores, (4) Conclusion: The OHRQoL is significantly limited in patients with OLP, especially, patients with erosive-ulcerative OLP are affected.

BACKGROUND Arterial hypertension (HT) is a leading cause of cardiac hypertrophy and heart failure. Ubiquitin-specific peptidase 18 (USP18) has been recently described as a factor that prevents myocardial dysfunction. The present study measured serum USP18 levels in normotensive (n=29), isolated diastolic hypertensive (n=20), and systolic-diastolic hypertensive (n=30) male participants and correlated these results with biochemical parameters that are included in routine assessments of patients with hypertension. MATERIAL AND METHODS Seventy-nine men, aged 24 to 82 years (mean=50.8±11.4 years), were included in the study. None of the participants had ever been treated for HT. Blood and urine parameters were assessed using routine techniques. Serum USP18 levels were measured by enzyme-linked immunosorbent assay. RESULTS The means and 95% confidence intervals (CIs) of USP18 levels in the HT(-), iDHT(+), and HT(+) groups were 69.3 (22.1-116.5) pg/ml, 90.1 (29.0-151.3) pg/ml, and 426.7 (163.1-690.3) pg/ml, respectively. In the HT(+) group, the mean serum USP18 level was 6.2-times higher than in the HT(-) group (p=0.014) and 4.7-times higher than in the iDHT(+) group (p=0.19). The partial correlation analysis that was adjusted for risk factors of arteriosclerosis indicated that USP18 levels were correlated with systolic blood pressure, pulse pressure, and heart rate. CONCLUSIONS This preliminary study found that serum USP18 levels were significantly higher in drug-naive male participants with arterial hypertension compared with normotensive controls. USP18 exerts cardiovascular-protective effects. Elevations of USP18 levels may indicate a counterregulatory process that is engaged during increases in pressure in the left ventricle.

Background The bone thickness of the human mandibular ramus is an important parameter in mandibular surgeries. The aim of this study was to systematically measure the bicortical bone thickness, the ramus dimensions and the position of the lingula. The measurements were tested on significant correlations to the patients’ parameters. Methods Based on CBCT scans 150 rami were reconstructed as 3D polygon surfaces. An anatomical grid was adapted to the ramus surface to mark the bone thickness measurement points and to achieve comparability between the measurements on different mandibles. The bone thickness, ramus height, ramus width and the gonion angle were measured. A cluster analysis was performed with these parameters to identify clinically relevant groups with anatomical similarities. Results The median distribution of the bone thickness was calculated and visualized in a pseudo-colour map. The mean ramus height was 44.78 mm, the mean width was 31.31 mm and the mean gonion angle was 124.8°. The average distance from the lingula to the dorsal tangent was 53% of the total width and its distance to the caudal tangent was 65% of the total height. Significant correlations between the bone thickness and the ramus proportions could be identified. Age and sex had no significant influence on the mean bone thickness. The measured rami could be divided into two groups by cluster analysis. Conclusion The dimensions of the human mandibular ramus can be determined from 3D reconstructed surface models from CBCT scans. Measurements could be made comparable by applying an anatomically oriented grid. A cluster analysis allowed the differentiation of two groups with different bone thickness distributions and geometries, which can be used for the optimization of osteosynthesis systems and their precision of adaptation to different ramus morphologies.

A fundamental step for cell growth and differentiation is the cell adhesion. The purpose of this study was to determine the adhesion of different cell lineages, adipose derived stromal cells, osteoblasts, and gingival fibroblast to titanium and zirconia dental implants with different surface treatments. Primary cells were cultured on smooth/polished surfaces (titanium with a smooth surface texture (Ti-PT) and machined zirconia (ZrO2-M)) and on rough surfaces (titanium with a rough surface texture (Ti-SLA) and zirconia material (ZrO2-ZLA)). Alterations in cell morphology (f-actin staining and SEM) and in expression of the focal adhesion marker were analysed after 1, 7, and 14 days. Statistical analysis was performed by one-way ANOVA with a statistical significance at p = 0.05. Cell morphology and cytoskeleton were strongly affected by surface texture. Actin beta and vimentin expressions were higher on rough surfaces (p &lt, 0.01). Vinculin and FAK expressions were significant (p &lt, 0.05) and increased over time. Fibronectin and laminin expressions were significant (p &lt, 0.01) and did not alter over time. Strength of cell/material binding is influenced by surface structure and not by material. Meanwhile, the kind of cell/material binding is regulated by cell type and implant material.

Aims Epidemiological studies found a link between aircraft noise exposure and increased incidence of arterial hypertension and cardiovascular disease, but the underlying pathophysiological mechanisms are not fully understood. Clinical studies have shown that mental stress affects the systemic and renal haemodynamic, but no such study was performed with noise exposure as stress factor. We analysed systemic and renal effects of 25 min standardized aircraft noise in a sham controlled clinical study including 80 healthy men and 34 male patients with hypertension. Methods and results Systemic haemodynamic parameters were measured using electrocardiography and impedance cardiography. The renal haemodynamic was assessed using steady state input clearance with infusion of para-aminohippuric acid and inulin for glomerular filtration rate and renal plasma flow, respectively. In the systemic circulation of hypertensive patients, there was an increase in total peripheral resistance (TPR) (1420 ± 387 vs. 1640 ± 516 dyn·s·cm−5, P = 0.001) and a decrease in cardiac index (CI) (2.9 ± 0.8 vs. 2.6 ± 0.8 L/(min·m2, P Conclusions In hypertensive but not healthy men we observed a systemic vasoconstrictive response after aircraft noise exposure accompanied by a decrease in CI. No significant changes were observed in the renal circulation. Our results suggest that male hypertensive patients are more susceptible for noise-induced changes of vascular resistance in the systemic circulation.

Summary Background Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. Methods In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov , NCT02439749 . Findings From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was −3·9 mm Hg (Bayesian 95% credible interval −6·2 to −1·6) and for office systolic blood pressure the difference was −6·5 mm Hg (−9·6 to −3·5). No major device-related or procedural-related safety events occurred up to 3 months. Interpretation SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. Funding Medtronic.

Background: Post-operative hypoxemia is prevalent in hospitalized patients and may adversely affect recovery. However, little data exist on the post-discharge phase or details on duration, severity and potential risk factors. Thus, we investigated the incidence and risk factors for severe desaturation during the first post-operative week after THA/TKA by continuous nocturnal oxygen saturation monitoring. Methods: The study was a secondary analysis of a prospective cohort study of 112 patients undergoing fast-track THA/TKA. Patients with known sleep apnoea were excluded. Oxygen saturation and heart rate were recorded by a wireless wrist-worn pulse oximeter 2 nights before and 7 nights after surgery. Data on demographics, opioid consumption and cognitive function were collected from medical charts, patient diaries and clinical testing respectively. The primary outcome was occurrence of severe desaturation defined as periods with saturation

Background: In hemodialysis (HD) patients cardiovascular events represent the predominant cause of mortality. Since platelet and monocyte activity markers play an important role in cardiovascular mortality, this study assessed the influence of HD on these markers. Methods: Forty one HD patients (25 male, 16 female) were included. Blood samples were obtained before and after a single HD session at baseline and again after an elapsed period of 114 ± 21 days (91–175 days) on maintenance hemodialysis. Surface expression of CD40L and CD62P on platelets, tissue factor binding on monocytes and platelet-monocyte aggregates were measured by flow cytometry. Plasma levels of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFa) and soluble CD40L were analyzed by enzyme linked immunosorbent assay. Results: Tissue factor on monocytes was significantly increased after a single HD session at baseline (p = 0.041), whereas platelet-monocyte aggregates, the expression of CD40L and CD62P on platelets did not change significantly. After a mean of 114 ± 21 days of HD therapy, tissue factor on monocytes (p < 0.0001), platelet-monocytes aggregates (p < 0.0001), plasma levels of MCP-1 (p = 0.012) and TNFa (p = 0.046) were significantly decreased compared to baseline values. In contrast, platelet surface expression of CD40L and CD62P as well as plasma levels of sCD40L and IL-6 were not attenuated significantly. There was no significant correlation detected between the markers examined and the cumulative time on hemodialysis. Conclusions: Platelet and monocyte activity markers assessed in this study do not appear to be significantly increased by HD therapy. Therefore, these markers probably cannot be accountable for increased cardiovascular mortality in chronic HD patients.

Although reduced early physical function after total hip- and knee arthroplasty (THA/TKA) is well-described, the underlying reasons have not been clarified with detailed studies on pathophysiological mechanisms related to recovery, thereby prohibiting advances in rehabilitation. Thus, we aimed to describe early post-THA/TKA physical activity measured by actigraphy and potential underlying pathophysiological mechanisms related to recovery in a well-defined cohort of THA and TKA patients. Daytime-activity was measured from 2 days before until 13 (THA) or 20 (TKA) days after surgery. The primary outcome was individualized recovery in activity, with secondary analyses of activity-intensities and association to the perioperative factors: sex, age, BMI, hemoglobin (hgb), C-reactive protein and postoperative pain. Eighty-one THA/TKA-patients were examined. A large inter-individual variation in early physical activity was found. On a group level, activity was significantly reduced compared to preoperatively the first 2 (THA) or 3 (TKA) weeks after surgery (mean-difference - 64 counts × 10 3/day, p

Background Primary failure of eruption (PFE) is a rare disease defined as incomplete tooth eruption despite the presence of a clear eruption pathway. Orthodontic extrusion is not feasible in this case because it results in ankylosis of teeth. To the best of our knowledge, besides the study of Ahmad et al. (Eur J Orthod 28:535-540, 2006), no study has systematically analysed the clinical features of and factors associated with PFE. Therefore, the aim of this study was to systematically evaluate the current literature (from 2006 to 2017) for new insights and developments on the aetiology, diagnosis, genetics, and treatment options of PFE. Methods Following the PRISMA guidelines, a systematic search was performed using the PubMed/Medline database for studies reporting on PFE. The following terms were used: “primary failure of tooth eruption”, “primary failure of eruption”, “tooth eruption failure”, and “PFE”. Results Overall, 17 articles reporting clinical data of 314 patients were identified. In all patients, the molars were affected. In 81 reported cases, both the molars and the premolars were affected by PFE. Further, 38 patients’ primary teeth were also affected. In 27 patients, no family members were affected. Additional dental anomalies were observed in 39 patients. A total of 51 different variants of the PTH1R gene associated with PFE were recorded. Conclusions Infraocclusion of the posterior teeth, especially if both sides are affected, is the hallmark of PFE. If a patient is affected by PFE, all teeth distal to the most mesial tooth are also affected by PFE. Primary teeth can also be impacted; however, this may not necessarily occur. If a patient is suspected of having PFE, a genetic test for mutation in the PTH1R gene should be recommended prior to any orthodontic treatment to avoid ankylosis. Treatment options depend on the patient’s age and the clinical situation, and they must be evaluated individually.

Sclerosing odontogenic carcinoma (SOC) is a primary intraosseous carcinoma of the jaws that has been listed as a separate entity for the first time in the latest version of the World Health Organization classification of Head and Neck Tumours (2017). The aim of this study was to analyse and interpret the existing literature on SOC in the context of a clinical case treated in the authors' department. A systematic search of the PubMed database was performed in accordance with the PRISMA guidelines, yielding nine cases of SOC reported so far. In summary, characteristic clinical and radiological features of SOC include asymptomatic swelling, location predominantly in the mandible, tumour primarily lytic in appearance, presence of cortical bone destruction, and lack of metastatic spread. Due to the rarity of the disease, close collaboration between oral/maxillofacial surgeons and pathologists is crucial to avoid misdiagnosis. With complete excision, no recurrence of SOC should be expected.

Background: Psychiatric conditions and psychopharmacological treatments have been demonstrated to be important risk-factors for prolonged hospital length of stay, readmission and morbidity, following fast-track total hip (THA) and total knee arthroplasty (TKA). Aims: The aim of the study was to provide a detailed description of the preoperative psychiatric characteristics of a well-defined patient population undergoing THA and TKA, using the 90-item Symptom Checklist (SCL-90-R). Methods: A pre-surgical population of 2183 patients completed the full SCL-90-R prior to THA/TKA from 2015 to 2016. The SCL-90-R scale and total scores of the pre-surgical sample were compared to the scores of an age- and gender stratified Danish sample of healthy controls. A Mokken scalogram analysis was conducted to assess the scalability of the SCL-90-R in both samples. Results: The Mokken analysis yielded acceptable scalability coefficients above 0.30 in all subscales of the SCL-90-R except psycoticism (0.28). There was no clinically significant difference (effect size =

Aims The purpose of this study was to assess early physical function after total hip or knee arthroplasty (THA/TKA), and the correlation between patient-reported outcome measures, physical performance and actual physical activity (measured by actigraphy). Patients and Methods A total of 80 patients aged 55 to 80 years undergoing THA or TKA for osteoarthritis were included in this prospective cohort study. The main outcome measure was change in patient reported hip or knee injury and osteoarthritis outcome score (HOOS/KOOS) from pre-operatively until post-operative day 13 (THA) or 20 (TKA). Secondary measures were correlations to objectively assessed change in physical performance (paced-walk, chair-stand, stair-climb tests) at day 14 (THA) or 21 (TKA) and actual physical activity (actigraphy) measured at day 12 and 13 (THA) or 19 and 20 (TKA). Results Patients reported improved physical function (HOOS or KOOS) pre-operatively until day 13 (THA) or 20 (TKA) with a mean difference of 7 (95% confidence interval (CI) 1 to 13, p = 0.033) and 6 (95% CI 1 to 12, p = 0.033) percentage points, respectively. By contrast, objectively assessed physical function and activity declined, with no correlations between subjective and objective assessments for either THA or TKA patients (r2 ≤ 0.16, p ≥ 0.314). Conclusions Early improvement in patient-reported physical function after THA/TKA does not correlate with objectively assessed function, and patient reported outcomes should not be used as the only measure of recovery. Cite this article: Bone Joint J 2017;99-B:1167–75

Study objective Postoperative cognitive dysfunction (POCD) remains a frequent postoperative complication in non-fast-track surgeries, with negative implications for return to daily activities and work. In fast-track total hip and -knee arthroplasty (THA/TKA) an 8–9% incidence of POCD after 3 months has been reported, but without details on specific perioperative risk factors. Thus, we re-investigated the incidence and role of suggested factors for POCD in a well-controlled patient cohort, to guide future preventive interventions. Design A subanalysis of a prospective study. Setting Hospital ward, patients own home. Patients One-hundred-and-four patients undergoing elective THA/TKA. Interventions A full contextual and validated cognitive test battery pre- and 2–3 weeks postoperatively by interview by research nurse. Measurements Results from the cognitive test battery were corrected for learning effect by normative data from an age-matched unoperated control group. Potential perioperative risk factors (age, procedure, gender, inflammation, blood-percentage, opioids etc.) associated with POCD was investigated by univariate and multivariate logistic analysis, with a 5% significance level. Main results Four patients (3.9%) developed POCD. POCD-positive patients consumed higher dose of opioids in the acute postoperative period (postoperative days 0–3: median 214 mg), vs. POCD-negative patients (postoperative days 0–3: median 98 mg, p = 0.008), and during the 2–3-week study period (POCD-positive vs. POCD-negative patients, median 739 mg vs. 208 mg, respectively). Other pre and postoperative factors were non-significant but associated with the development of POCD. Conclusion POCD is rare in fast-track THA/TKA patients and may be related to postoperative opioid consumption, supporting the ongoing focus on opioid-sparing analgesia.

In Germany, around four million people are affected by a rare disease, from which 15% show orofacial manifestations.The aim of this cross-sectional study was to determine the oral health-related quality of life of people with rare diseases and to investigate the relationship between oral symptoms, diagnostic delay, and gender.A questionnaire with open-ended questions, including questions from the validated oral health impact profile (OHIP) G14 questionnaire, was developed to survey the subjective oral health-related quality of life. The questionnaire was sent to 125 German member associations of the umbrella organization of self-help groups. The correlation between OHIP values and the three factors was evaluated using a regression model with a significance level of p = 0.01.In total, 473 participants affected by 96 different rare diseases were included in this analysis. The OHIP value for participants without oral manifestations was 6.54 points lower than for those with oral symptoms (p = 0.001). For oral symptoms, the OHIP increased by 0.080 points (p = 0.014) with each year of diagnostic delay. A connection with sex was not found.Regardless of the presence of oral symptoms, people with rare diseases in Germany show a poorer oral health-related quality of life than is known to the normal population. If oral symptoms are present, they show a negative correlation with oral health-related quality of life. On average, it takes 8.37 years for a disease to be correctly diagnosed. The earlier a rare disease is diagnosed, the better the oral health-related quality of life of those affected.

INTRODUCTION: There has been an increased focus on fast-track (FT) programmes and the potential to convert unicompartmental knee replacement (UKR) from short-term admission to outpatient surgery. However, relatively few studies have been presented and with differences in selection criteria and completion rates. The purpose of this study was to describe patient selection and completion rates in a patient group undergoing UKR in two high-volume FT knee surgery clinics. METHODS: All consecutive patients (n = 368) referred to and selected for UKR were screened for eligibility for outpatient surgery with discharge on the day of surgery (DOS). Reasons why the patients were not discharged were recorded in patients not completing the outpatient pathway, and readmissions and complications were recorded until three months post-operatively. RESULTS: Among all referred and screened patients, 69% were considered eligible for outpatient surgery. DOS discharge occurred in 59% of the operated patients and in 37% of all referred and screened patients. Main reasons for why patients were not discharged were active wound drainage and lack of mobilisation due to pain, nausea and vomiting. Two patients were readmitted during the first 24 hours due to wound drainage. One patient had a lung embolus and one patient an acute myocardial infarction during the follow-up period. CONCLUSIONS: This study illustrates that not all patients in a consecutive patient group for UKR were feasible for outpatient surgery. Further studies should focus on optimising pain treatment and reducing post-operative nausea.none. TRIAL REGISTRATION: not relevant.

Background The compound letermovir (LMV) has recently been approved for the prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV seropositive recipients of an allogeneic hematopoietic stem cell transplant. LMV inhibits CMV replication by binding to the viral terminase complex. However, first cases of clinical LMV resistance have been occurred. Here we report a fast breakthrough of resistant cytomegalovirus during secondary LMV prophylaxis in a hematopoietic-cell transplant recipient. Case presentation A 44-year-old male patient with acute myeloid leukemia (AML) experienced a CMV-reactivation within the first 4 weeks of allogeneic hematopoietic-cell transplantation. Administration of LMV was initiated at day + 34. Due to increasing viral loads, LMV treatment was discontinued after 8 days. The patient was then administered with valganciclovir (valGCV) until viral DNA was undetectable. Due to neutropenia, valGCV treatment was switched to LMV secondary prophylaxis. For 4 weeks, the patient maintain virologic suppression. Then, CMV viral loads increased with a fast kinetic. Genotypic testing of the viral polymerase UL54, the kinase UL97 as well as the viral terminase UL56 and UL89 revealed the mutation C325Y in UL56, which is associated with the high level LMV resistance. Conclusion It is known that Letermovir is approved for prophylactic purposes. However, it may be used for some patients with CMV infection who either have failed prior therapies or are unable to tolerate other anti-CMV compounds. Particularly, the administration of LMV should be avoided in patients with detectable viral loads. When this is not possible, viral load must be routinely monitored along with UL56 genotyping. Furthermore, LMV administration at high virus loads may foster the rapid selection of resistant CMV mutants.

Background: Ectodermal dysplasia describes a heterogeneous group of hereditary, congenital malformations involving developmental dystrophies of ectodermal structures. The aim of this study was to analyse the oral health-related quality of life (OHRQoL) in people with ectodermal dysplasia and to evaluate the influence of different variables. Methods: The study was designed as an anonymous epidemiological survey study among people with ectodermal dysplasia to evaluate oral symptoms, satisfaction with the health system and their respective OHRQoL using the validated German version of the OHIP-14 (Oral Health Impact Profile) questionnaire. Results: When asked about oral symptoms, 110 of the participants provided responses, of which 109 (99.09%) described oral symptoms. The average age of the female participants at the time of diagnosis was 17.02 years (range: 0 to 48 years), the average age of men was 5.19 years (range: 0 to 43 years). The average OHIP-14 overall score for female participants was 12.23 points (SD: 12.39), for male participants an average OHIP score of 11.79 points was recorded (SD: 11.08 points). Difficulty in finding a dentist (p = 0.001), and the dissatisfaction with the health system (p = 0.007) showed a negative impact on the OHRQoL. Conclusion: People with ectodermal dysplasia rate their OHRQoL worse than is usually prevalent in the normal German population (4.09 points), women are diagnosed with &ldquo, ectodermal dysplasia&rdquo, later than men. Participants who reported difficulties in finding a dentist for treatment exhibited higher OHIP values. Likewise, dissatisfaction with the health system demonstrated a negative impact on the oral health-related quality of life.

Background and Objectives: Salmonellosis is a major foodborne bacterial infection throughout the world. Epidemiological surveillance is one of the key factors to reduce the number of infections caused by this pathogen in both humans and animals. The first outcome measure was the prevalence of non-typhoid Salmonella (NTS) infections between 2000 and 2017 among the population of the predominantly agricultural and touristic Polish region of Warmia and Masuria (WaM). The second outcome measure was the comparison of the NTS hospitalization rate of all registered NTS cases, an investigation of the monthly reports of infections, and the exploration of the annual minimal and maximal NTS infection number in WaM in the above-mentioned time period. The last outcome was a comparison of the prevalence of NTS infections in the region and in its administrative districts by considering both rural and urban municipalities three years before and three years after the accession of Poland into the European Union (EU) in 2004. Materials and Methods: The total number of infections and hospitalizations in the 19 districts of the WaM voivodship in Poland was registered monthly between 2000&ndash, 2017 by the Provincial Sanitary-Epidemiological Station in Olsztyn, Poland. Results: Between 2000 and 2017, the number of diagnosed salmonellosis cases decreased significantly in WaM, the decrease was higher in urban districts than in rural ones, and the ratio of hospitalizations and the total number of NTS cases increased significantly across all districts. The lowest number of cases was reported in the winter months and was stable from 2007, whereas the highest number was reported in the summer months with a higher tendency of outbreaks. Conclusion: The falling number of salmonellosis cases in 2000&ndash, 2017 in WaM reflects the general trend in Poland and Europe. The decrease of NTS infections in WaM is related to the accession of Poland into the EU.

Background Empagliflozin has been shown to reduce cardiovascular mortality, but the underlying pathogenetic mechanisms are poorly understood. It was previously demonstrated that empagliflozin improved arterial stiffness. Methods Our analysis comprising 58 patients with type 2 diabetes mellitus identifies factors triggering the improvement of arterial stiffness. All patients participated in an investigator-initiated, prospective, double-blind, randomized, placebo-controlled, interventional clinical trial (http://www.ClinicalTrials.gov: NCT02471963, registered 15th June 2015, retrospectively registered) and received either 6-weeks treatment with 25 mg empagliflozin orally once daily or placebo (crossover). Central systolic pressure and central pulse pressure were recorded by the SphygmoCor System (AtCor Medical). Now, we investigated the impact of parameters of glucose metabolism, volume status, sympathetic activation, lipids, uric acid, blood pressure and inflammation on vascular parameters of arterial stiffness using multivariate regression analysis. Results As previously reported, therapy with empagliflozin improved arterial stiffness as indicated by reduced central systolic blood pressure (113.6 ± 12.1 vs 118.6 ± 12.9 mmHg, p Conclusion Besides age and sex, change in systolic 24-h ambulatory blood pressure and change in hsCRP were determinants of the empagliflozin induced improvement of vascular parameters of arterial stiffness, whereas parameters of change in glucose metabolism and volume status had no significant influence. Our analysis suggests that empagliflozin exerts, at least to some extent, its beneficial vascular effects via anti-inflammatory mechanisms. Trial registrationhttp://www.ClinicalTrials.gov: NCT02471963, registered 15th June 2015, retrospectively registered

Background The primary purpose of this study was to collect data on the oral health-related quality of life (OHRQoL) of individuals with x-linked hypophosphatemia (XLH). It was also designed to gather information on the period of diagnosis, oral symptoms, orthodontic therapy, and satisfaction with dental care and the healthcare system. Methods A questionnaire was developed to evaluate the OHRQoL consisting of open-ended questions and the standardised German version of the Oral Health Impact Profile-14 (OHIP-14). Results The questionnaires from 43 participants were analysed, including 32 females (74.41%) and 11 males (25.59%). The mean OHIP-14 total score for the combined genders was 10.30 points (range: 0–37 points). For the combined genders, the mean period of time that elapsed between the first signs of the illness and the diagnosis was 5.52 years (range: 0–49 years). In total, 77.50% of the participants described oral symptoms, such as tooth mineralisation defects (n = 26), abscess or fistula formation (n = 21), dysgnathia (n = 9) and temporomandibular dysfunction (n = 2). The correlation between the participants’ satisfaction with the healthcare system and the OHIP-14 values was weak (− 0.21), and it was not statistically significant (p = 0.199). Conclusions The majority of the study participants reported oral involvement in the context of XLH, especially dental hard tissue mineralisation disorders, abscess formation and fistula formation. Those individuals affected by XLH with oral manifestations exhibited a tendency toward a worse OHRQoL than those without oral symptoms. In Germany, the OHIP-14 scores for these XLH patients were worse than those values that were obtained from the general population. Electronic supplementary material The online version of this article (10.1186/s13005-019-0192-x) contains supplementary material, which is available to authorized users.

PURPOSE To evaluate the effects of different titanium particle concentrations on viability of human calvarial osteoblasts and human gingival fibroblasts. MATERIALS AND METHODS Primary human calvarial osteoblasts (HCO, 3H Biomedical) and human gingival fibroblasts (HGF-1, ATCC) were cultivated and allowed to adhere for 24 hours. Titanium powder concentrations (0.01 to 1.0 mg/mL) were added, and samples were analyzed at three time points (24 hours, 7 days, 21 days). Cell viability was analyzed using living cell count, proliferation (MTT) assay, and a live/dead staining. Cytotoxic effects were evaluated using lactated dehydrogenase assay. Qualitative analysis of cell viability was performed. In addition, scanning electron microscopy (SEM) analysis was performed. Release of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-±) was estimated with Human IL-6 / Human TNF-± ELISA. RESULTS Titanium concentrations of 0.1 mg/mL and 1.0 mg/mL showed medium- and long-term effects on cell growth and proliferation rates. Cytotoxic effects by release of lactate dehydrogenase were observable during the first 24 hours. Human gingival fibroblast cells showed a release factor between 2.6 to 3.4. Titanium powder seemed to be more cytotoxic to human gingival fibroblast cells than to human calvarial osteoblast cells. For human calvarial osteoblasts, only the highest concentration showed cytotoxic effects with a release factor of 2.7. Human calvarial osteoblasts secreted IL-6 only during the first 24 hours and only in the highest titanium concentration, whereas human gingival fibroblasts secreted IL-6 during the entire period. The lowest titanium concentration showed stronger secretion of IL-6 compared to control. Incorporation of smaller and single titanium particles by cells was identified under SEM analysis. CONCLUSION Cell viability is negatively correlated with titanium concentration. Further, titanium debris might lead to an inflammatory biologic response of dental peri-implant tissue. Also, cells interact with the debris, eg, with incorporation of particles.

For the guided regeneration of periimplant hard and soft tissues, human adipose-derived stromal cells (hADSC) seem to be a promising source for mesenchymal stromal cells. For this, the proliferation and differentiation of hADSC were evaluated on titanium and zirconia dental implants with different surface treatments. Results were compared to edaphic cells as human osteoblasts (hOB) and human gingival fibroblasts (HGF). Primary cells were cultured on (1) titanium implants with a polished surface (Ti-PT), (2) sandblasted and acid-etched titanium (Ti-SLA), (3) sandblasted and alkaline etched zirconia (ZrO2-ZLA) and (4) machined zirconia (ZrO2-M). The cell proliferation and differentiation on osteogenic lineage were assessed after 1, 7 and 14 days. Statistical analysis was performed by one-way ANOVA and a modified Levene test with a statistical significance at p = 0.05. PostHoc tests were performed by Bonferroni-Holm. Zirconia dental implants with rough surface (ZrO2-ZLA) showed the highest proliferation rates (p = 0.048). The osteogenic differentiation occurred early for zirconia and later for titanium implants, and it was enhanced for rough surfaces in comparison to polished/machined surfaces. Zirconia was more effective to promote the proliferation and differentiation of hADSCs in comparison to titanium. Rough surfaces were able to improve the biological response for both zirconia and titanium.

Background and Objective: The oral health-related quality of life (OHRQoL) of patients with achalasia has not been evaluated to date. Therefore, the aim of this study was to assess the OHRQoL of patients with achalasia and to get information about the time taken for diagnosis and oral symptoms. Materials and Methods: The study was conceived of as an anonymous epidemiological survey study in people with achalasia in order to assess their OHRQoL in each case. For this, a questionnaire was developed consisting of free-text questions and of the standardized German version of the OHIP-14 questionnaire. Results: In total, forty-four questionnaires were analyzed including 31 female and 13 male participants. Regardless of gender, the mean age was 50.57 years (range: 17&ndash, 78). Of the surveyed individuals, seventy-nine-point-five-five percent had been diagnosed between 25 and 60 years of age. The period from the first signs of the disease to diagnosis was 6.15 years, irrespective of gender. The overall OHIP-14 score without gender differentiation was 8.72 points (range 0&ndash, 48), the mean score of female participants was 11.13 (range: 0&ndash, 48), and the OHIP score of male participants was 3.15 on average. Two participants reported oral symptoms. Conclusions: The already known problem of the delayed diagnosis of rare diseases was also confirmed in the case of achalasia. Females with achalasia seemed to be significantly affected by lower OHRQoL than males with achalasia and women of the general population. Demineralization of the tooth structure was described in two participants.

Background: The aim of this study was to analyze data on oral health-related quality of life (OHRQoL) in people with Marfan syndrome and to obtain information on the diagnosis period, orthodontic treatment, and oral symptoms. Methods: A questionnaire was developed consisting of open questions and the standardized German version of the OHIP-14 (Oral Health Impact Profile) questionnaire for the evaluation of OHRQoL. The age of diagnosis, time period from the first signs of the disease to diagnosis, and OHIP-values were compared between male and female participants. Additionally, the OHIP-values between participants who were orthodontically treated and those who were not treated were assessed. The statistical analysis was performed using the Mann&ndash, Whitney test with a significance level at p = 0.05. Results: A total of 51 questionnaires were evaluated, which included 34 female and 17 male participants. Overall, 84% of respondents reported oral symptoms. Male respondents tended to diagnose the disease earlier (p = 0.00), with a smaller period between the first symptom and the diagnosis (p = 0.04). The OHIP-14 score was gender-neutral at 13.65 &plusmn, 13.53 points. Conclusion: In Marfan syndrome, many years (12.01 &plusmn, 11.61) elapse between the onset of first symptoms and correct diagnosis of the disease. People with Marfan syndrome have a worse OHRQoL than do the general population.

Background Adult stem cells appear to be a promising subject for tissue engineering, representing an individual material for regeneration of aged and damaged cells. Especially adipose derived stromal cells (ADSC), which are easily to achieve, allow an encouraging perspective due to their capability of differentiating into miscellaneous cell types. Here we describe the in vitro formation of human subcutaneous, visceral and omental ADSC micromasses and compare their histological attributes while being cultivated on collagen membranes. Methods Subcutaneous, visceral and omental fat tissue derived cells were isolated and processed according to standard protocols. Positively stained cells for CD13, CD44 and CD90 were cultivated on agarose in order to study micromass formation using a special method of cell tracking. Stained paraffin-embedded micromasses were analysed morphologically before and after being plated on collagen membranes. Results The micromass formation process was similar in all three tissue types. Subcutaneous fat tissue derived micromasses turned out to develop a more homogeneous and compact shape than visceral and omental tissue. Nevertheless all micromasses adhered to collagen membranes with visible spreading of cells. The immune histochemical (IHC) staining of subcutaneous, visceral and omental ADSC micromasses shows a constant expression of CD13 and a decrease of CD44 and CD 90 expression within 28 days. After that period, omental fat cells don’t show any expression of CD44. Conclusion In conclusion micromass formation and cultivation of all analysed fat tissues can be achieved, subcutaneous cells appearing to be the best material for regenerative concepts.

Objective: In patients with resistant hypertension, percutaneous placement of an iliac arteriovenous coupler device leads to a reduction of blood pressure (BP) via decreased total vascular resistance and improved arterial compliance. However, long-term efficacy and safety need to be further explored. We report on the first case of 3.5-year follow-up in a patient who underwent implantation of an iliac arteriovenous coupler device. Results: A patient with resistant hypertension was admitted to hospital. Despite treatment with six anti-hypertensive drugs, his BP was poorly controlled. Previously, he had undergone renal denervation, which did not cause a significant BP decrease. Therefore, an arteriovenous coupler device was implanted, leading to an immediate and significant BP decrease. The patient was discharged with an office BP of 122/71 mmHg. After 3 months, there was a sustained BP decrease (−14/9 mmHg), whereas later, it was fluctuant (office BP: 147–173/85–95 mmHg, ABPM: 153–166/81–94 mmHg) probably due to medication non-adherence confirmed by a urinary toxicological screening test. Follow-up right heart catheterization showed changes in hemodynamic parameters related to volume congestion, which were accompanied by progressive dyspnea and weight gain. This was controlled by an optimized diuretic therapy. Additionally, an invasive closure maneuver was performed, leading to an immediate BP increase after closure and a similar decrease after re-opening of the anastomosis, verifying its proper long-term function. Conclusion: The implantation of an iliac arteriovenous coupler device appears to be a promising and effective method to decrease BP and therefore reduce cardiovascular risk in patients with severe, treatment-resistant hypertension.

Background: The aim of this study was to examine the current dental care situation in Germany from the perspective of those affected by a rare disease, especially concerning their satisfaction with the German dental health care system, and thus assess the relationship between their perspective and their oral health-related quality of life (OHRQoL). Methods: A questionnaire regarding their experiences with the dental assistance and the health care system, such as the OHIP-14, was sent to the member associations of the organization of self-help groups for rare diseases ACHSE e.V. The correlation between OHIP-14 values and patient&rsquo, s perspective was statistically analyzed by the non-parametric Tau de Kendall test (p &lt, 0.05). Results: There was a statistically significant correlation between the OHIP score and the patient&rsquo, s perspective regarding dental assistance and health care system (p &lt, 0.05). For those surveyed who were satisfied with the support of the health care system, an average OHIP score of 8.54 &plusmn, 10.45 points (range: 0&ndash, 48) was determined. The group that did not feel sufficiently supported by the health care system had an average OHIP score of 16.07 &plusmn, 13.43 points (range: 0&ndash, 56). Discussion: The majority of respondents with rare diseases are dissatisfied with the German health care system and its support with regard to dental care.

In 2013, a national action plan for people with rare diseases (Nationaler Aktionsplan für Menschen mit Seltenen Erkrankungen, NAMSE) was adopted in the Federal Republic of Germany which is currently in the implementation phase. People with rare diseases are often confronted with huge difficulties in the diagnosis and therapy, and being repeatedly misdiagnosed also leads to psychological stress for those affected and their families. Of the up to 8000 rare diseases, about 15% can manifest in the orofacial region and thus give an indication of the underlying disease. A look in the oral cavity or consultative support to determine the cause of symptoms in the oral and maxillofacial region can possibly help the specialists in internal medicine to find the appropriate diagnosis.

Background The Interdisciplinary Tumor Board (ITB) of the Cooperative Ewing Sarcoma Study (CESS) Group was investigated to assess its impact on the overall survival (OAS) of Ewing sarcoma (EwS) patients. The ITB functions as a reference center for the international institutions participating in the clinical trials of the CESS group, but is also available internationally to patients who have not been treated within an appropriate clinical trial. The value of tumor boards in terms of benefit for the patients and the health care system in general is not well documented and is also the subject of controversial discussions. A review of the representative literature is included. Methods Data were analyzed from 481 patients who had been registered into the European Ewing Tumor Working Initiative of National Groups (EURO E.W.I.N.G.-99) clinical trial via the CESS data center between 2006 and 2009; this included 331 patients with localized disease and another 150 individuals with metastases at diagnosis. Median follow-up time was 3.2 years. Results Improved OAS was observed for patients with metastases who had received recommendations from the ITB compared with those who had not received recommendations. In patients with localized disease, a recommendation from the ITB had no influence on OAS. Conclusion As a reference center for a rare disease, recommendations from our ITB impacted local therapy and led to higher OAS in patients with metastatic disease. To our knowledge, this is the first analysis that examines the value of a reference tumor board on a rare disease.

The aim of this study was to evaluate the biocompatibility of two comparatively new calcium silicate containing sealers (MTA-Fillapex and BioRoot-RCS) with that of two established sealers (AH-Plus, epoxy resin-based; Pulp-Canal-Sealer, zinc oxide eugenol containing). Human periodontal ligament cells (PDL-cells) were brought in contact with eluates from freshly mixed and set sealer. The sealers were mixed strictly according to the manufacturers’ instructions and identically samples were produced. 1:1, 1:2, and 1:10 dilutions of sealers extract were used. Extracts from freshly mixed sealer were added to the PDL-cells on day one to simulate a clinical scenario. Subsequently, at 24 h, 7, 14, and 21 days extracts form set sealers were used for PDL-cell culturing. PDL-cell viability was analyzed by living-cell-count, MTT-assay, and living/dead-staining, cytotoxicity by LDH-assay, and changes by Richardson-staining. All data were statistically evaluated by one way ANOVA and a posthoc analysis with Bonferroni-Holm testing (p

In 2013 the German Ministry of Health initiated a "National Plan of Action for People with Rare Diseases" (NAMSE), in order to improve medical treatment for people with rare diseases. The aim of NAMSE is to set up appropriate medical care for those affected, as well as to obtain information on the current state of care for these patients. The aim of this study was to obtain information on the oral health-related quality of life (OHRQoL) of people with rare diseases with oral involvement.In the context of the NAMSE plan, special consultation times were introduced for people with rare diseases with oral involvement. Using the standardized OHIP 14 questionnaire, specific information was acquired on OHRQoL, as was as general information on the disease in question.During consultation hours, 50 people were treated who, on average, travelled 143 km each way. On average, patients had to wait 5 years before the final diagnosis of their rare disease was reached. The mean OHIP 14 overall score achieved was 26.4.The long distances travelled show the effort involved for patients, especially for those who come for a series of sessions. This has led to a call for a nationwide system of special consultation sessions for rare diseases with oral involvement - something NAMSE has also called for. There seems to be a markedly worse OHRQoL among all our patients. Overall, rare diseases with oral involvement appear to benefit more from an earlier diagnosis of the disease than do rare diseases without any oral involvement.Um die medizinische Versorgung von Menschen mit Seltenen Erkrankungen (SE) zu verbessern wurde 2013 durch das Bundesministerium für Gesundheit ein „Nationaler Aktionsplan für Menschen mit Seltenen Erkrankungen“ (NAMSE) ins Leben gerufen. Ziel des NAMSE ist dabei, eine medizinisch adäquate Versorgung für die Betroffenen aufzubauen sowie Informationen über die aktuelle Versorgungssituation von SE zu gewinnen. Vor diesem Hintergrund sollen Informationen zur die mundgesundheitsbezogenen Lebensqualität (OHRQoL) bei Menschen mit SE und oraler Beteiligung gewonnen werden.Unter dem Hintergrund des NAMSE wurde eine Spezialsprechstunde für SE mit oraler Beteiligung eingerichtet. Mittels dem standardisiertem OHIP-14 Fragebogen wurden Informationen zur OHRQoL sowie allgemeine Informationen zur Erkrankung gewonnen.Insgesamt wurden 50 Patienten in der Sprechstunde behandelt. Diese nahmen durchschnittlich eine einfache Anfahrtsstrecke von 143 km auf sich. Im Mittel mussten die Betroffenen 5 Jahre auf die finale Diagnose ihrer SE warten. Die Betroffenen weisen einen durchschnittlichen OHIP-14 Gesamt-Score von 26,4 auf. SCHLUßFOLGERUNG: Der lange Anfahrtsweg zeigt, welchen Aufwand Patienten insbesondere bei mehrfachen Vorstellungen auf sich nehmen müssen. Hieraus entsteht die Forderung, künftig flächendeckend Spezialsprechstunden für SE mit oraler Beteiligung aufzubauen, wie dies auch im NAMSE gefordert wird. Der Vergleich mit den wenigen vorhandenen Daten lässt auf eine deutlich schlechtere OHRQoL in unserem Patientenkollektiv schließen. Seltene Erkrankungen mit oraler Beteiligung scheinen insgesamt von einer früheren Diagnose der Erkrankung zu profitieren, als SE ohne orale Beteiligung.

On November 25, the first national congress for rare diseases in dentistry and oral medicine under the auspices of ACHSE e. V. and Orphanet was held in Muenster. With speakers from the field of medicine, dentistry, politics, patient advocacy groups, self-help groups and persons concerned, a platform for exchange between physicians and patients on an equal footing was offered to the participants. At the end of each of the 12 lectures, more than 300 national and international guests discussed the various issues and perspectives related to the topic of rare diseases in dentistry and oral medicine. Besides the different presentations focusing on dentistry, neuropediatrics, and human genetics, the existing centers for rare diseases, sources of information, European reference networks, and the national action plan for people with rare diseases were the subjects of intensive discussion. The patient perspective was also considered. From now on the congress shall be held in Muenster biennially.