Determination of the androgen receptor status of disseminated tumor cells in primary breast cancer patients.

PURPOSE: Androgen receptor (AR) can serve as a new therapeutic target since it was shown to play a proliferative role in several breast cancer (BC) subtypes. Moreover, AR positivity has been suggested to reflect the metastatic potential of tumor cells in some BC subtypes. The aim of this study was to determine the AR expression on disseminated tumor cells (DTCs) as a surrogate marker of minimal residual disease (MRD) and potential precursor of metastasis in early BC. METHODS: Bone marrow (BM) aspirates from 62 DTC-positive early BC patients were included into this study and analyzed by immunofluorescence staining for the presence of AR-positive DTCs. CK-positive, CD45-negative cells containing an intact nucleus (DAPI positive) were identified as DTCs. AR expression of the primary tumor (PT) was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded (FFPE) tumor sections from core biopsies and surgical specimens. RESULTS: AR status of DTCs could be determined in 21 patients. We detected AR-positive DTCs in nine samples (43%). AR expression of DTCs and corresponding PT showed a concordance rate of 33%. The DTC-AR status did not correlate with clinicopathological factors, nor did we observe a significant correlation between the AR status of the PT and other established prognostic factors for BC. CONCLUSION: AR-positive DTCs can be detected in BM of early BC patients with a marked discordance of the AR status between DTCs and corresponding PTs. The clinical significance of these findings needs further investigation.

A novel approach to determining augmented bone volume in intraoral bone block augmentation using an intraoral scanner: an in vitro study.

INTRODUCTION: Bone augmentation procedures are established tools for reshaping the alveolar ridge and increasing bone volume. Different approaches are being used to measure postoperative bone volume gain. This study aimed to develop an objective and automated volume measurement tool equally as precise as manual slice-by-slice annotation. MATERIALS AND METHODS: To evaluate the proposed workflow, we performed an in vitro study with 20 pig mandibles that were grafted using three different grafting techniques-autogenous full block, split block bone and shell augmentation. The pig jaws were scanned pre- and postoperatively using an intraoral scanner. The resulting surface files (baseline, full block, split block, shell) were processed using the new volume-measuring workflow as well as using manual slice-by-slice annotation at baseline (t0) and at 6 months (t1) using the same population. Two TOSTs (Test of One-Sided Significance) and NHSTs (Null Hypothesis Significance Test) were used to compare the two workflows. The intra-rater reliability between t0 and t1 was determined using intraclass correlation coefficients. RESULTS: The mean difference for the full block augmentation technique was - 0.015 cm3 (p < 0.001); for the split block technique, it was - 0.034 cm3 p = 0.01, and for the shell technique, it was - 0.042 cm3. All results were statistically not different from zero and statistically equivalent to zero. The results also showed an excellent absolute intra-rater agreement. CONCLUSIONS: The semiautomatic volume measurement established in this article achieves comparable results to manual slice-by-slice measuring in determining volumes on STL files generated by intraoral scanners and shows an excellent intra-rater reliability.

A critical assessment of the medication-related osteonecrosis of the jaw classification in stage I patients: a retrospective analysis

Objectives@#It is unclear whether the extent of intraoral mucosa defects in patients with medication-related osteonecrosis of the jaw indicates disease severity. Therefore, this study investigated whether mucosal lesions correlate with the true extent of osseous defects in stage I patients. @*Materials and Methods@#Retrospectively, all patients with stage I medication-related osteonecrosis of the jaw who underwent surgical treatment between April 2018 and April 2019 were enrolled. Preoperatively, the extent of their mucosal lesions was measured in clinical evaluations, and patients were assigned to either the visible or the probeable bone group. Intraoperatively, the extent of necrosis was measured manually and with fluorescence. @*Results@#Fifty-five patients (36 female, 19 male) with 86 lesions (46 visible bone, 40 probeable bone) were enrolled. Intraoperatively, the necrotic lesions were significantly larger (P<0.001) than the preoperative mucosal lesions in both groups. A significant (P<0.05) but very weak (R 2 <0.2) relationship was noted between the extent of the mucosal lesions and the necrotic bone area. @*Conclusion@#Preoperative mucosal defects (visible or probeable) in patients with medication-related osteonecrosis of the jaw do not indicate the extent of bone necrosis or disease severity.

A critical assessment of the medication-related osteonecrosis of the jaw classification in stage I patients: a retrospective analysis

Objectives@#It is unclear whether the extent of intraoral mucosa defects in patients with medication-related osteonecrosis of the jaw indicates disease severity. Therefore, this study investigated whether mucosal lesions correlate with the true extent of osseous defects in stage I patients. @*Materials and Methods@#Retrospectively, all patients with stage I medication-related osteonecrosis of the jaw who underwent surgical treatment between April 2018 and April 2019 were enrolled. Preoperatively, the extent of their mucosal lesions was measured in clinical evaluations, and patients were assigned to either the visible or the probeable bone group. Intraoperatively, the extent of necrosis was measured manually and with fluorescence. @*Results@#Fifty-five patients (36 female, 19 male) with 86 lesions (46 visible bone, 40 probeable bone) were enrolled. Intraoperatively, the necrotic lesions were significantly larger (P<0.001) than the preoperative mucosal lesions in both groups. A significant (P<0.05) but very weak (R 2 <0.2) relationship was noted between the extent of the mucosal lesions and the necrotic bone area. @*Conclusion@#Preoperative mucosal defects (visible or probeable) in patients with medication-related osteonecrosis of the jaw do not indicate the extent of bone necrosis or disease severity.

Head motion during cone-beam computed tomography: Analysis of frequency and influence on image quality

Purpose@#Image artifacts caused by patient motion cause problems in cone-beam computed tomography (CBCT) because they lead to distortion of the 3-dimensional reconstruction. This prospective study was performed to quantify patient movement during CBCT acquisition and its influence on image quality. @*Materials and Methods@#In total, 412 patients receiving CBCT imaging were equipped with a wireless head sensor system that detected inertial, gyroscopic, and magnetometric movements with 6 dimensions of freedom. The type and amplitude of movements during CBCT acquisition were evaluated and image quality was rated in 7 different anatomical regions of interest. For continuous variables, significance was calculated using the Student t-test. A linear regression model was applied to identify associations of the type and extent of motion with image quality scores. Kappa statistics were used to assess intra- and inter-rater agreement. Chi-square testing was used to analyze the impact of age and sex on head movement. @*Results@#All CBCT images were acquired in a 10-month period. In 24% of the investigations, movement was recorded (acceleration: >0.10 [m/s2 ]; angular velocity: >0.018 [°/s]). In all examined regions of interest, head motion during CBCT acquisition resulted in significant impairment of image quality (P0.7). @*Conclusion@#Relevant head motions during CBCT imaging were frequently detected, leading to image quality loss and potentially impairing diagnosis and therapy planning. The presented data illustrate the need for digital correction algorithms and hardware to minimize motion artefacts in CBCT imaging.

Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort.

BACKGROUND: The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Polymorphisms in genes regulating inflammation may explain part of the genetic heritage. METHODS: Using a candidate gene approach, 39 mainly functional single nucleotide polymorphisms (SNPs) in 26 genes regulating inflammation were assessed in a clinical homogeneous group of severely diseased patients consisting of 624 patients with CD, 411 patients with UC and 795 controls. The results were analysed using logistic regression. RESULTS: Sixteen polymorphisms in 13 genes involved in regulation of inflammation were associated with risk of CD and/or UC (p ≤ 0.05). The polymorphisms TLR2 (rs1816702), NFKB1 (rs28362491), TNFRSF1A (rs4149570), IL6R (rs4537545), IL23R (rs11209026) and PTPN22 (rs2476601) were associated with risk of CD and the polymorphisms TLR2 (rs1816702), TLR4 (rs1554973 and rs12377632), TLR9 (rs352139), LY96 (rs11465996), NFKBIA (rs696), TNFA (rs1800629), TNFRSF1A (rs4149570), IL10 (rs3024505), IL23R (rs11209026), PTPN22 (rs2476601) and PPARG (rs1801282) were associated with risk of UC. When including all patients (IBD) the polymorphisms TLR2 (rs4696480 and rs1816702), TLR4 (rs1554973 and rs12377632), TLR9 (rs187084), TNFRSF1A (rs4149570), IL6R (rs4537545), IL10 (rs3024505), IL23R (rs11209026) and PTPN22 (rs2476601) were associated with risk. After Bonferroni correction for multiple testing, both the homozygous and the heterozygous variant genotypes of IL23R G>A(rs11209026) (OR(CD,adj): 0.38, 95% CI: 0.21-0.67, p = 0.03; OR(IBD,adj) 0.43, 95% CI: 0.28-0.67, p = 0.007) and PTPN22 1858 G>A(rs2476601) (OR(CD,unadj) 0.54, 95% CI: 0.41-0.72, p = 7*10-4; OR(IBD,unadj): 0.61, 95% CI: 0.48-0.77, p = 0.001) were associated with reduced risk of CD. CONCLUSION: The biological effects of the studied polymorphisms suggest that genetically determined high inflammatory response was associated with increased risk of CD. The many SNPs found in TLRs suggest that the host microbial composition or environmental factors in the gut are involved in risk of IBD in genetically susceptible individuals.

Current concepts in diagnosis and treatment of venous malformations.

INTRODUCTION: Venous malformations are the most common type of vascular malformation, usually detected at birth or during puberty. By occurring during human growth or through localized trauma, pain, functional impairment and aesthetic disfigurement is often observed. Ultrasonography, Doppler flow Imaging, and Magnetic Resonance Imaging are the most informative techniques which reveal the extent of tissue involvement and differentiate between high and low flow anomalies. Therapeutic options for treatment of venous malformations are sclerotherapy with alcohol, ethoxysclerol and bleomycin, laser therapy (Nd:YAG), surgery and combined therapeutic modalities. The aim of percutaneous sclerotherapy is the successive reduction of the volume of the lesion by aseptic inflammation. PATIENTS AND METHODS: This is a review of 51 patients with venous malformation treated by the Interdisciplinary Center for Vascular Anomalies at the University Hospital Tübingen, (Germany), from July, 2002 until January, 2007. The mean age of first consultation in our outpatient department was 26.4 years (median). 12 patients were treated by sclerotherapy with highly concentrated alcohol, 9 by surgery, and 7 by laser therapy. In some cases we combined different treatments. 9 patients had only sclerotherapy, while 3 had a combination of pre-operative sclerotherapy and surgery. RESULTS: We obtained positive results in patients treated with sclerotherapy and combined sclerotherapy and surgery. CONCLUSION: Sclerotherapy is safe (under fluoroscopic control), efficient, and can be repeated multiple times. Therefore, it should be considered as first-line treatment in venous malformations. A combination of a sclerotherapy with surgery is also useful in many cases.

Activation Markers CD63 and CD203c Are Upregulated in Chronic Urticaria

No abstract available.

The Influence of IgE on Cultured Human Mast Cells

PURPOSE: The mast cell plays a pivotal role in the human immune response. Crosslinking of 2 IgE molecules bound to the high affinity IgE receptor (FcepsilonRI) on the surface of the mast cell results in mast cell degranulation and the release of several proinflammatory mediators. Patients with type-I allergy have increased levels of IgE in the blood compared to healthy individuals. METHODS: In a 6-week culture system of stem cells to human mast cells we investigated the effect of the concentration of IgE. The mast cells were cultured with different concentrations of IgE for the last 10 days of the maturation period. It was observed how the IgE concentration affects the histamine release, FcepsilonRI density on the mast cell surface and the concentration of other mediators. RESULTS: A clear correlation between IgE concentration in culture medium and the release of histamine upon activation was observed. It showed a bell-shaped dose response curve, with maximal response around an IgE-concentration of 250 ng/mL. Furthermore, the sensitivity of the mast cells and surface density of FcepsilonRI on mast cell surface was also influenced by the IgE concentration in the culture medium. CONCLUSIONS: IgE in the culture medium during the last 10 days of mast cell maturation influences the release of the preformed mediator histamine after mast cell activation and the density of FcepsilonRI on the mast cell surface. The release of the de novo synthetized mediator prostaglandin D2 and the expression of chymase and tryptase are not influenced by IgE in culture medium.

The Influence of IgE on Cultured Human Mast Cells

PURPOSE: The mast cell plays a pivotal role in the human immune response. Crosslinking of 2 IgE molecules bound to the high affinity IgE receptor (FcepsilonRI) on the surface of the mast cell results in mast cell degranulation and the release of several proinflammatory mediators. Patients with type-I allergy have increased levels of IgE in the blood compared to healthy individuals. METHODS: In a 6-week culture system of stem cells to human mast cells we investigated the effect of the concentration of IgE. The mast cells were cultured with different concentrations of IgE for the last 10 days of the maturation period. It was observed how the IgE concentration affects the histamine release, FcepsilonRI density on the mast cell surface and the concentration of other mediators. RESULTS: A clear correlation between IgE concentration in culture medium and the release of histamine upon activation was observed. It showed a bell-shaped dose response curve, with maximal response around an IgE-concentration of 250 ng/mL. Furthermore, the sensitivity of the mast cells and surface density of FcepsilonRI on mast cell surface was also influenced by the IgE concentration in the culture medium. CONCLUSIONS: IgE in the culture medium during the last 10 days of mast cell maturation influences the release of the preformed mediator histamine after mast cell activation and the density of FcepsilonRI on the mast cell surface. The release of the de novo synthetized mediator prostaglandin D2 and the expression of chymase and tryptase are not influenced by IgE in culture medium.