Analysis of Genes Related to Invadopodia Formation and CTTN in Oral Squamous Cell Carcinoma-A Systematic Gene Expression Analysis.

Successful treatment for any type of carcinoma largely depends on understanding the patterns of invasion and migration. For oral squamous cell carcinoma (OSCC), these processes are not entirely understood as of now. Invadopodia and podosomes, called invadosomes, play an important role in cancer cell invasion and migration. Previous research has established that cortactin (CTTN) is a major inducer of invadosome formation. However, less is known about the expression patterns of CTTN and other genes related to it or invadopodia formation in OSCC during tumor progression in particular. In this study, gene expression patterns of CTTN and various genes (n = 36) associated with invadopodia formation were analyzed to reveal relevant expression patterns and give a comprehensive overview of them. The genes were analyzed from a whole genome dataset of 83 OSCC samples relating to tumor size, grading, lymph node status, and UICC (Union for Internatioanl Cancer Control). The data revealed significant overexpression of 18 genes, most notably CTTN, SRC (SRC proto-onocogene, non-receptor tyrosine kinase), EGFR (epidermal growth factor receptor), SYK (spleen associated tyrosine kinase), WASL (WASP like actin nucleation promotion factor), and ARPC2 (arrestin beta 1) due to their significant correlation with further tumor parameters. This study is one of the first to summarize the expression patterns of CTTN and related genes in a complex group of OSCC samples.

Influence of marginal incision and Le Fort I osteotomy on periodontal tissues: a prospective longitudinal study.

The purpose of this prospective study was to evaluate whether the surgical protocol involving marginal incision and Le Fort I osteotomy affects the periodontal outcome. Twenty-nine patients requiring surgical correction of maxillary dysgnathia were selected for this study. Periodontal conditions of maxillary anterior teeth were assessed prior to the surgery (T0), one month (T1), and 6 months (T2) after the surgical procedure. Interdental papillae loss, periodontal parameters and aesthetic outcomes in the anterior zone were assessed. Statistical analysis was performed with Friedman´s test and within ANOVA (p ≤ 0.05) followed by post-hoc tests. Papilla height decreased from T0 to T1 (p = 0.003), followed by an increase from T1 to T2 (p = 0.040). PPD (T0 = 1.72 ± 0.46; T2 = 2.13 ± 0.43) and CAL (T0 = 1.24 ± 0.55; T2 = 1.99 ± 0.70) increased after 6 months. There were statistically significant differences in aesthetic score among T0, T1 and T2. Periodontal changes after orthognathic surgery were within acceptable biological levels. Although a change in papillae height was reported after the surgery, initial values were recovered after 6 months. Surgical incision design might improve the outcome of Le-Fort I osteotomy. Anterior aesthetic zone may benefit from a marginal incision design, as it respects vascularization principle and may ensure a wound healing without complications.

Effect of Cold Atmospheric Plasma (CAP) on Osteogenic Differentiation Potential of Human Osteoblasts.

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.

Epithelioid Rhabdomyosarcoma at the High Parietal Area of the Head: A Case Report.

Epithelioid rhabdomyosarcoma is a rare condition, which may be clinically misinterpreted as melanoma due to its morphological appearance. Careful morphological and immunohistochemical analysis play an important role in its diagnosis. This case report describes the clinicopathological features of an epithelioid RMS diagnosed at the high parietal area of the head. A 71-year-old male patient presented a red-brown pigmented ulcerative nodule in the high parietal region of the head. Previous biopsy and computer tomography imaging revealed a malignant melanoma in stage I (pT2, sN0, Mx). After tumor operation, histological and immunohistochemical analysis of the tumor were conducted. Histological analysis showed an erosive lesion with a monomorphic cell population containing small cells with prominent nucleoli. A positivity was confirmed for CD10, Vimentin, and Desmin. MyoD1 was detected, as well as a fluctuating signal for p53. Molecular analysis revealed a negativity for Sox-10, and a weak positivity for CK8/18 by absence of p40. Based on the morphological and immunohistochemical findings, the tumor was diagnosed as epithelioid RMS.

Renal hemodynamic effects differ between antidiabetic combination strategies: randomized controlled clinical trial comparing empagliflozin/linagliptin with metformin/insulin glargine.

BACKGROUND: Type 2 diabetes causes cardio-renal complications and is treated with different combination therapies. The renal hemodynamics profile of such combination therapies has not been evaluated in detail. METHODS: Patients (N = 97) with type 2 diabetes were randomized to receive either empagliflozin and linagliptin (E+L group) or metformin and insulin glargine (M+I group) for 3 months. Renal hemodynamics were assessed with para-aminohippuric acid and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR). Intraglomerular hemodynamics were calculated according the Gomez´ model. RESULTS: Treatment with E+L reduced GFR (p = 0.003), but RPF remained unchanged (p = 0.536). In contrast, M+I not only reduced GFR (p = 0.001), but also resulted in a significant reduction of RPF (p < 0.001). Renal vascular resistance (RVR) decreased with E+L treatment (p = 0.001) but increased with M+I treatment (p = 0.001). The changes in RPF and RVR were different between the two groups (both padjust < 0.001). Analysis of intraglomerular hemodynamics revealed that E+L did not change resistance of afferent arteriole (RA) (p = 0.116), but diminished resistance of efferent arterioles (RE) (p = 0.001). In M+I group RA was increased (p = 0.006) and RE remained unchanged (p = 0.538). The effects on RA (padjust < 0.05) and on RE (padjust < 0.05) differed between the groups. CONCLUSIONS: In patients with type 2 diabetes and preserved renal function treatment with M+I resulted in reduction of renal perfusion and increase in vascular resistance, in contrast to treatment with E+I that preserved renal perfusion and reduced vascular resistance. Moreover, different underlying effects on the resistance vessels have been estimated according to the Gomez model, with M+I increasing RA and E+L predominantly decreasing RE, which is in contrast to the proposed sodium-glucose cotransporter 2 inhibitor effects. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov (NCT02752113) on April 26, 2016.

Detection of Changes in Renal Blood Flow Using Arterial Spin Labeling MRI.

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.

Association of Noise Annoyance with Measured Renal Hemodynamic Changes.

BACKGROUND: Chronic mental stress is recognized as a modifiable risk factor for cardiovascular disease. The aim of this study was to demonstrate that noise annoyance-induced stress is associated with changes in renal hemodynamics. METHODS: Renal hemodynamic parameters were measured using steady-state input clearance with infusion of para-aminohippuric acid and inulin in individuals with normal, high normal, and elevated blood pressure. All individuals ranked subjective annoyance due to noise in everyday life on a 7-grade Likert scale. The median of all rankings was used as a cutoff point to divide the group into noise-annoyed and non-noise-annoyed individuals. Different renal hemodynamic parameters were calculated based on the Gomez equation. RESULTS: Noise-annoyed individuals (n = 58) showed lower renal plasma flow (599 ± 106 vs. 663 ± 124 mL/min, p = 0.009), lower renal blood flow (1,068 ± 203 vs. 1,172 ± 225 mL/min, p = 0.047), higher filtration fraction (22.7 ± 3.3 vs. 21.3 ± 3.0, p = 0.012), higher renal vascular resistance (88.9 ± 25.6 vs. 75.8 ± 22.9 mm Hg/[mL/min], p = 0.002), and higher resistance of afferent arteriole (2,439.5 ± 1,253.4 vs. 1,849.9 ± 1,242.0 dyn s-1 cm-5, p = 0.001) compared to non-noise-annoyed individuals (n = 55). There was no difference in measured glomerular filtration rate (133 ± 11.8 vs. 138 ± 15 mL/min, p = 0.181), resistance of efferent arteriole (2,419.4 ± 472.2 vs. 2,245.8 ± 370.3 dyn s-1 cm-5, p = 0.060), and intraglomerular pressure (64.0 ± 3.1 vs. 64.6 ± 3.5 mm Hg, p = 0.298) between the groups. After adjusting for age, renal plasma flow, renal blood flow, and renal vascular resistance remained significantly different between the groups, with a trend in increased afferent arteriolar resistance and filtration fraction. CONCLUSION: In this study, noise annoyance was associated with reduced renal perfusion attributed to increased renal vascular resistance predominantly at the afferent site. Long-term consequences of this renal hemodynamic pattern due to noise annoyance need to be investigated.

Biocompatibility of Lithium Disilicate and Zirconium Oxide Ceramics with Different Surface Topographies for Dental Implant Abutments.

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 < 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.

Clinical characteristics of oral lichen planus and its causal context with dental restorative materials and oral health-related quality of life.

BACKGROUND: The aim of this study was to investigate the influence of clinical characteristics and dental restorative materials on oral health-related quality of life in patients with oral lichen planus. In particular, the influences of amalgam and metals were investigated. METHODS: A total of 112 patients with clinical and histological features of oral lichen planus from the Department of Cranio-Maxillofacial Surgery at the University Hospital of Münster participated in this prospective study. Clinical parameters of oral lichen planus and the dental restorative materials used were evaluated. Oral health-related quality of life was investigated by using the short form of the German version of the Oral Health Impact Profile (OHIP-14). In addition, physical pain was rated on a visual analogue scale. RESULTS: The average OHIP-14 score was 13.54. A high correlation was seen between OHIP and pain. Likewise, higher OHIP-values were seen for male patients, and such as for those patients with non-reticular forms of oral lichen planus (OLP). A local form of OLP is more often seen on female patients, such as with the presence of reticular lichen. In regard to the restorations, the presence of composite restorations is correlated with a local lichen, whereas the presence of gold restorations is often seen with a generalized lichen. Furthermore, the grading of strength of association between mucosal lesion and amalgam/metal was tested. No significant differences revealed the analysis of the relationship between gender, clinical form of OLP, age, and presentation form between the 4 gradings of Thornhill. CONCLUSIONS: The oral health-related quality of life is significantly limited in patients with oral lichen planus. But these OHIP scores are not influenced by the restorative materials. Here, pain severity is the most important aspect. We found no statistical differences in the clinical parameters between patients with amalgam or metal restoration and patients without these restorations. It is not necessary to replace amalgam fillings that are not in direct contact with mucosal surfaces.

Feasibility and Safety of CD19 Chimeric Antigen Receptor T Cell Treatment for B Cell Lymphoma Relapse after Allogeneic Hematopoietic Stem Cell Transplantation.

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.

Relationship Between Ubiquitin-Specific Peptidase 18 and Hypertension in Polish Adult Male Subjects: A Cross-Sectional Pilot Study.

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.

Three-Dimensional Planning of the Mandibular Margin in Hemifacial Microsomia Using a Printed Patient-Specific Implant.

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.

Influence of Implant Material and Surface on Mode and Strength of Cell/Matrix Attachment of Human Adipose Derived Stromal Cell.

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 < 0.01). Vinculin and FAK expressions were significant (p < 0.05) and increased over time. Fibronectin and laminin expressions were significant (p < 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.

State of knowledge about information sources and health care centres for rare diseases among affected people in Germany.

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.

Oral Health-Related Quality of Life in People with Achalasia.

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: 17-78). 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 0-48); the mean score of female participants was 11.13 (range: 0-48), 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.

How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial.

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 < 0.001), central pulse pressure (39.1 ± 10.2 vs 41.9 ± 10.7 mmHg, p = 0.027) forward (27.1 ± 5.69 vs 28.7 ± 6.23 mmHg, p = 0.031) as well as reflected wave amplitude (18.9 ± 5.98 vs 20.3 ± 5.97 mmHg, p = 0.045) compared to placebo. The multivariate regression analysis included age, sex and change between empagliflozin and placebo therapy of the following parameters: HbA1c, copeptin, hematocrit, heart rate, LDL-cholesterol, uric acid, systolic 24-h ambulatory blood pressure and high sensitive CRP (hsCRP). Besides the influence of age (beta = - 0.259, p = 0.054), sex (beta = 0.292, p = 0.040) and change in systolic 24-h ambulatory blood pressure (beta = 0.364, p = 0.019), the change of hsCRP (beta = 0.305, p = 0.033) emerged as a significant determinant of the empagliflozin induced reduction in arterial stiffness (placebo corrected). When replacing HbA1c with fasting plasma glucose in the multivariate regression analysis, a similar effect of the change in hsCRP (beta = 0.347, p = 0.017) on arterial stiffness parameters was found. 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 registration http://www.ClinicalTrials.gov : NCT02471963, registered 15th June 2015, retrospectively registered.

Performance of BeGraft and BeGraft+ Stent-Grafts as Bridging Devices for Fenestrated Endovascular Aneurysm Repair: An In Vitro Study.

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<0.001). The shear stress test showed median forces of 10.5 vs 15.28 N at 150% of the stent diameter for the 6-mm BeGraft and BeGraft+ stent-grafts, respectively, and 15.23 vs 20.72 N at 150% stent diameter for the 8-mm models (p=0.016 and 0.017, respectively). Conclusion: Flaring changed the stent geometry but did not provoke stent fractures. The BeGraft+ is superior to the BeGraft in terms of pullout and shear stress forces, demonstrating greater resilience.

Fast breakthrough of resistant cytomegalovirus during secondary letermovir prophylaxis in a hematopoietic stem cell transplant recipient.

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.

[Oral Health-Related Quality of Life in Rare Diseases with Oral Manifestations]. / Evaluierung der mundgesundheitsbezogenen Lebensqualität bei seltenen Erkrankungen mit oraler Beteiligung.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Evaluation of the biocompatibility of root canal sealers on human periodontal ligament cells ex vivo.

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 < 0.05). In contact with BioRoot-RCS a regeneration of the PDL-cells were observed over time. This sealer showed the lowest toxicity in a freshly mixed and set state (p < 0.05). MTA-Fillapex and Pulp-Canal-Sealer were cytotoxic in a fresh as well as in a set state, whereas AH-Plus was cytotoxic in a freshly mixed state, but not when the sealer was set. BioRoot-RCS is biocompatible and bioactive because it seems to have a positive influence on the PDL-cell metabolism. Pulp Canal Sealer and MTA-Fillapex showed no biocompatibility in contact with PDL-cells at all. Freshly mixed AH Plus is less biocompatible on PDL than in a set state.