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Objective: To design a patient-specific subperiosteal implant for a severely atrophic maxillary ridge using yttria-stabilized additively manufactured zirconia (3YSZ) and evaluate its material properties by applying topology optimization (TO) to replace bulk material with a lattice structure., Materials: A contrast-based segmented skull model from anonymized computed tomography data of a patient was used for the initial anatomical design of the implant for the atrophic maxillary ridge. The implant underwent finite element analysis (FEA) and TO under different occlusal load-bearing conditions. The resulting implant designs, in bulk material and lattice, were evaluated via in-silico tensile tests and 3D printed., Results: The workflow produced two patient-specific subperiosteal designs: a) an anatomically precise bulk implant, b) a TO lattice implant. In-silico tensile tests revealed that the Young's modulus of yttria-stabilized zirconia is 205 GPa for the bulk material and 83.3 GPa for the lattice. Maximum principal stresses in the implant were 61.14 MPa in bulk material and 278.63 MPa in lattice, both tolerable, indicating the redesigned implant can withstand occlusal forces of 125-250 N per abutment. Furthermore, TO achieved a 13.10 % mass reduction and 208.71 % increased surface area, suggesting improved osteointegration potential., Significance: The study demonstrates the planning and optimization of ceramic implant topology. A further iteration of the implant was successfully implanted in a patient-named use case, employing the same fabrication process and parameters., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to assess implant survival and complications rate of modern subperiosteal implants (CAD designed and additively manufactured)., Methods: A systematic review was conducted using three electronic databases; Medline (Pubmed), Cochrane library, and SCOPUS, following the PRISMA statement recommendations to answer the PICO question: "In patients with bone atrophy (P), do additively manufactured subperiosteal implants (I), compared to subperiosteal implants manufactured following traditional approaches (c), present satisfactory implant survival and complication rates (O)? The study was pre-registered in PROSPERO (CRD42023424211). Included articles quality was assessed using the "NIH quality assessment tools"., Results: Thirteen articles were finally selected (5 cohort studies and 8 case series), including 227 patients (121 female / 106 male; weighted mean age 62.4 years) and 227 implants. After a weighted mean follow-up time of 21.4 months, 97.8% of implants were in function (5 failures reported), 58 implants (25.6%) presented partial exposure, 12 patients (5.3%) suffered soft tissue or persistent infection. Fracture of the interim prosthesis was reported in 8 of the155 patients (5.2%) in which the use of a provisional prosthesis was reported. A great heterogeneity was found in terms of study design and methodological aspects. For this reason, a quantitative analysis followed by meta-analysis was not possible., Conclusions: Within the limitations of this study, modern additively manufactured subperiosteal implants presented a good survival in the short-time, but a noticeable number of soft-tissue related complications were reported. Further studies are needed to assess the clinical behavior in the medium- and long-term., (© 2024. The Author(s).)

The aim of this study was to evaluate, if and with what accuracy perioperative blood loss can be calculated by a machine learning algorithm prior to orthognathic surgery. The investigators implemented a random forest algorithm to predict perioperative blood loss. 1472 patients who underwent orthognathic surgery from 01/2006 to 06/2017 at our institution were screened and 950 patients were included and separated 80%/20% in a training set - utilized to generate the prediction model - and a testing set - utilized to estimate the accuracy of the model. The outcome variable was the correlation between actual perioperative blood loss and predicted perioperative blood loss in the testing set. Other study variables were the difference of actual and predicted perioperative blood loss and important factors influencing perioperative blood loss using random forest feature importance. Descriptive and bivariate statistics were computed and the P value was set at 0.05. There was a statistically significant correlation between actual perioperative blood loss and predicted perioperative blood loss (p < 0.001). The mean difference was 7.4 ml with a standard deviation of 172.3 ml. The results of this study suggest that the application of a machine-learning algorithm allows a prediction of perioperative blood loss prior to orthognathic surgery., (Copyright © 2019 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: Genetic counseling and testing can be offered to individuals who are at high risk of carrying a breast cancer (BRCA) gene mutation. However, the content of genetic counseling could be difficult to understand due to complex medical information. The aim of this study was to investigate if comprehension can be improved with a new genetic counseling tool (NGCT hereafter; a tool that combines complex medical information with pictures, diagrams and tables) as compared to conventional oral-only genetic counseling (CGC)., Methods: 207 clients attended genetic counseling for hereditary breast and ovarian cancer at the Medical University of Vienna between February 2015 and February 2016. Seventy clients participated in this study and were allocated into two groups: the first 36 participants received conventional (oral only) genetic counseling (CGC) and the following 34 participants received genetic counseling using a new genetic counseling tool (NGCT), which combines complex information with pictures, diagrams and tables. After genetic counseling, all consenting participants were invited to complete a questionnaire with seven questions evaluating their comprehension of the medical information provided., Results: Socio-demographic backgrounds were comparable in both groups. Correct responses were significantly higher in the NGCT group compared to the CGC group (p = 0.012). NGCT also statistically improves correct response of Q1 (p = 0.03) and Q7 (p = 0.004)., Conclusion: The NGCT leads to an overall better understanding of the content of a genetic counseling session than CGC alone., Competing Interests: The authors have declared that no competing interests exist.

Gamma-glutamyltransferase (GGT) is an established marker for proliferative/apoptotic balance and has been associated with cancer risk and prognosis. The aim of this study was to evaluate the value of pre-treatment GGT serum levels as prognostic biomarker in patients with primary uterine leiomyosarcoma (ULMS). Data of women with ULMS were extracted from a multi-center database. Pre-treatment GGT serum levels were measured and patients assigned to predefined GGT risk groups. GGT values were correlated with clinico-pathological parameters and univariate and multivariable survival analyses were performed. A total of 44 patients with ULMS were analyzed. Mean (SD) pre-therapeutic GGT serum level was 33.8 (39.8) U/L. In Figo Stage I versus II-IV mean (SD) GGT values were 28.8 (34.0) U/l and 43.5 (49.2) U/l, respectively (p = 0.25). Five-year overall survival (OS) rates in ULMS patients with normal low versus higher GGT levels were 70% and 37%, respectively (p = 0.043). Univariate and multivariable analyses revealed that higher GGT serum levels (p = 0.043, p = 0.005) and high histological grade (p = 0.029, p = 0.012) were independently associated with impaired OS, respectively. Higher pre-treatment GGT serum levels were independently associated with unfavorable prognosis in women with ULMS. Thus, GGT seems to be a useful novel biomarker in ULMS.

Background: The purpose of this study was to evaluate socio-demographic characteristics of clients claiming genetic counseling for hereditary breast and ovarian cancer (HBOC) in Austria. Furthermore, changes of these parameters before and after Angelina Jolie's (AJ) disclosure of carrying a BRCA mutation were evaluated., Methods: In this prospective, nonrandomized study 268 consecutive clients seeking genetic counseling for HBOC at the Medical University of Vienna, Department of Obstetrics and Gynecology, Vienna, Austria between June 2012 and June 2014 were included. Socio-demographic data and source of information about HBOC and genetic counseling were evaluated. First, socio-demographic parameters were compared to the general Austrian population. Second, changes in these parameters after AJ's public disclosure of carrying a BRCA mutation were analyzed., Results: Subjects were more frequent female, younger and higher educated in comparison to Austria's general population (p < 0.001). Furthermore, level of education in participants was higher before than after AJ's disclosure (p = 0.046). Most clients were informed about genetic counseling by physicians. As expected, after AJ's public announcement patients were more frequent advised to genetic counseling by social media (p = 0.043) and family or friends (p = 0.010) than before., Conclusions: In this present study we could demonstrate that particularly younger and female participants with high educational level attended significantly more often genetic counseling for HBOC. Increased presence of HBOC in media since AJ's disclosure of carrying a BRCA mutation had lead that information and awareness about HBOC was obtained by a wider audience from different social background.

Objective: To describe the incidence of febrile neutropenia (FN) and use of pegfilgrastim in cancer patients with high overall risk of FN and to investigate the relationship between granulocyte-colony stimulating factor (G-CSF) guideline adherence and chemotherapy delivery in Central and Eastern Europe (CEE) and Austria., Methods: Dose Intensity Evaluation Program and Prophylaxis (DIEPP) was a multicentre, prospective, and observational study of adult patients with breast cancer, lymphoma, lung cancer, gastric cancer, and ovarian cancer, who received chemotherapy with pegfilgrastim support and who had an overall risk of FN ≥ 20 %. Physicians assessed patient risk factors and reported their reasons for administering pegfilgrastim., Results: Patients were enrolled from 113 centres in CEE and Austria between August 2010 and July 2013, and data were analysed from 1072 patients. The most common tumour types were breast cancer (50 %) and lymphoma (24 %). FN incidence was 5 % overall. FN occurred in 3 % of patients (28/875) who received pegfilgrastim as primary prophylaxis (PP) and 13 % of patients (19/142) who received it as secondary prophylaxis (SP); 79 % of FN events in SP patients occurred in the first cycle before pegfilgrastim was administered. The three most frequently chosen reasons for using pegfilgrastim were planned chemotherapy with high FN risk, female gender, and advanced disease. Overall, 40 % of patients received > 90 % of their planned chemotherapy dose within 3 days of the planned schedule., Conclusion: FN incidence was relatively low with pegfilgrastim PP in patients with a physician-assessed overall FN risk of ≥ 20 %. The most important reasons for pegfilgrastim use were consistent with the investigators' risk assessment and international guidelines.

Objective: C-reactive protein (CRP) has previously been shown to serve as a prognostic parameter in women with gynecologic malignancies. Due to the lack of valid prognostic markers for uterine leiomyosarcoma (ULMS) this study set out to investigate the value of pre-treatment CRP serum levels as prognostic parameter., Methods: Data of women with ULMS were extracted from databases of three Austrian centres for gynaecologic oncology. Pre-treatment CRP serum levels were measured and correlated with clinico-pathological parameters. Univariate and multivariable survival analyses were performed., Results: In total, 53 patients with ULMS were included into the analysis. Mean (SD) CRP serum level was 3.46 mg/dL (3.96). Solely, an association between pre-treatment CRP serum levels and tumor size (p = 0.04) but no other clinic-pathologic parameter such as tumor stage (p = 0.16), or histological grade (p = 0.07), was observed. Univariate and multivariable survival analyses revealed that CRP serum levels (HR 2.7 [1.1-7.2], p = 0.037) and tumor stage (HR 6.1 [1.9-19.5], p = 0.002) were the only independent prognostic factors for overall survival (OS) in patients with ULMS. Patients with high pre-treatment CRP serum levels showed impaired OS compared to women with low levels (5-year-OS rates: 22.6% and 52.3%, p = 0.007)., Conclusion: High pre-treatment CRP serum levels were independently associated with impaired prognosis in women with ULMS and might serve as a prognostic parameter in these patients.

Approximately 6-15 % of breast cancer patients are diagnosed with primary ulcerated breast cancer (ULBC). ULBC is known to be associated with short recurrence free and poor overall survival. Therefore, the purpose of this study was to characterize ULBC and compare the histopathological findings with those of non-ulcerative breast cancer (NULBC). A total of 152 ULBCs were evaluated and compared to 304 consecutive non-ulcerated, age-matched breast malignancies. Patients mean age was 65 years (SD = 13.0 ULBC, SD = 14.0 NULBC). ULBC was associated with a higher rate of poorly differentiated tumors (p = < 0.001), as well as larger tumor sizes (p = < 0.001). As expected, the rate of axillary lymph node involvement was higher in ULBC patients (p = <0.001). In addition to that, ULBC was associated with a higher rate of triple negative breast cancer (p = 0.002), and higher Ki67 expression (p = < 0.001). ULBC showed more aggressive histopathological features in comparison to NULBC which may contribute to the generally known poorer prognosis of women with ULBC.

Background: Gamma-glutamyltransferase (GGT) is a known marker for apoptotic balance and cell detoxification. Recently, an association of baseline GGT levels and breast cancer incidence, tumor progression and chemotherapy resistance was shown. The purpose of this study was to evaluate the association of pre-therapeutic GGT levels, clinical-pathological parameters and survival in patients with primary metastatic breast cancer (PMBC)., Methods: In this multicenter analysis, pre-therapeutic GGT levels and clinical-pathological parameters of 114 patients diagnosed with PMBC between 1996 and 2012 were evaluated. The association between GGT levels and clinical-pathological parameters were analysed. Patients were stratified into four GGT risk-groups (GGT < 18.00 U/L: normal low, 18.00 to 35.99 U/L: normal high, 36.00 to 71.99 U/L: elevated and ≥ 72.00 U/L: highly elevated) and survival analyses were performed., Findings: Patients in the high risk GGT group had a poorer overall survival, when compared to the low risk group with five-year overall survival rates of 39.5% and 53.7% (p = 0.04), respectively. Patients with larger breast tumors had a trend towards higher GGT levels (p = 0.053). Pre-therapeutic GGT levels were not associated with indicators of aggressive tumor biology such as HER2-status, triple negative histology, or poorly differentiated cancers., Conclusion: Pre-therapeutic GGT serum level might serve as a novel prognostic factor for overall-survival in patients with PMBC.

Objective: In addition to dysmenorrhea, dyspareunia, and subfertility, pain in the lower extremities has been described to be a further complaint in women affected by endometriosis, and lysis of nerve entrapment was thought to be associated with amelioration of leg pain. Therefore, we aimed to compare the prevalence of cyclic leg pain and pain intensity between women with endometriosis and without endometriosis, and to evaluate the effect of laparoscopic surgery., Study Design: Forty-four women with endometriosis and 58 controls were included in a prospective, controlled clinical trial at a University hospital/tertiary referral center. Participants were asked to complete questionnaires the day before and six to nine weeks after laparoscopy. The prevalence and intensity of leg pain and improvement after laparoscopic surgery, quantified according to a visual analog scale (VAS) score, were evaluated. We also recorded involvement of dermatomes, the presence and intensity of dysmenorrhea, and correlations between age, stage of endometriosis (rAFS-score), and preoperative VAS scores., Results: Before surgery, more women were affected by leg pain in the endometriosis group, compared to the control group (45.5% and 25.9%, respectively). Preoperative VAS scores for leg pain, however, were not significantly different between the two groups. A moderate correlation in the preoperative VAS scores between leg pain and dysmenorrhea was observed. After laparoscopy, we found a significant improvement in leg pain intensity in both groups. The mean difference in the VAS score for pain reduction between the study group and the control group was 0.74 (95% CI: -0.61-2.08), which was not statistically significant., Conclusions: The prevalence of leg pain is increased in endometriosis, while leg pain intensity is not, compared to women without endometriosis. Laparoscopic surgery-even without preparation and decompression of nerve tissue-is associated with an improvement in pain intensity in women with endometriosis, as well as in the group without endometriosis., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Endometriosis compromises the quality of life of countless women worldwide and is a leading cause of disability. Clinical symptoms of endometriosis can be very heterogeneous leading to a long interval between onset of symptoms and surgical diagnosis. A noninvasive, rapid diagnostic test is urgently needed. In this prospective study, we evaluated the usefulness of Cytokeratin-19 (CK19) as a biomarker for the diagnosis of endometriosis through urine and serum ELISA. 76 reproductive-aged women undergoing laparoscopy for benign conditions were included to this study and divided into two groups by the presence (n = 44) or absence (n = 32) of endometriosis. There was no statistically significant correlation between the concentration of CK19 in urine (p = 0.51) or in serum (p = 0.77) and the diagnosis of endometriosis. Assigning the samples to the proliferative or secretory cycle stage did not sufficiently lower the p values. In this study, the promising data reported in the recent literature about CK19 serving as a sufficient biomarker for endometriosis could not be verified when tested in a larger sample size. Further studies are warranted to explore the usefulness of CK19 in the diagnosis of endometriosis.

Ethnic differences in breast cancer are well described in studies comparing Hispanic and African-American populations to Caucasian populations. The aim of this study was to analyze the biological characteristics of breast cancer (BC) in the young Asian/Han Chinese population compared to Caucasians/Central Europeans. Histopathologies of 642 invasive BC in women at the age of 40 years and younger were analyzed in China and Austria. Pearson's chi-squared test was used to assess differences in the analyzed populations. Significantly larger BC >2 cm (p < 0.0001) and poorly differentiated BC (p = 0.02) as well as more triple-negative BC (p = 0.002) were identified among the Han Chinese group compared to the Central European group. This analysis will provide ethnic-specific insight into the biological characteristics of BC in young patients worldwide.

Although the use of (neo-)adjuvant chemotherapy in breast cancer patients has resulted in improved outcome, not all patients benefit equally. We have evaluated the utility of an in vitro chemosensitivity assay in predicting response to neoadjuvant chemotherapy. Pre-therapeutic biopsies were obtained from 30 breast cancer patients assigned to neoadjuvant epirubicin 75 mg/m2 and docetaxel 75 mg/m2 (Epi/Doc) in a prospectively randomized clinical trial. Biopsies were subjected to a standardized ATP-based Epi/Doc chemosensitivity assay, and to gene expression profiling. Patients then received 3 cycles of chemotherapy, and response was evaluated by changes in tumor diameter and Ki67 expression. The efficacy of Epi/Doc in vitro was correlated with differential changes in tumor cell proliferation in response to Epi/Doc in vivo (p = 0.0011; r = 0.73670, Spearmańs rho), but did not predict for changes in tumor size. While a pre-therapeutic gene expression signature identified tumors with a clinical response to Epi/Doc, no such signature could be found for tumors that responded to Epi/Doc in vitro, or tumors in which Epi/Doc exerted an antiproliferative effect in vivo. This is the first prospective clinical trial to demonstrate the utility of a standardized in vitro chemosensitivity assay in predicting the individual biological response to chemotherapy in breast cancer.

Background: BRCA-1/2 germline mutations are responsible for early onset breast cancer and familial association. The underlying causes of the characteristic phenotypic behavior are not completely understood, but mammary stem cells appear to have a key role in this process., Materials and Methods: We have investigated the presence of mammary stem / progenitor cells in normal tissues and in tumor tissues obtained from women with and without BRCA1/2 germline mutations by utilizing ALDH-1 immunohistochemistry., Results: Isolated ALDH-1 positive cells were found in 15/28 (54%) of breast cancer samples from women with BRCA 1 or 2 mutations and in 33 /51 (65%) of matched sporadic breast cancer cases (p=0.5949, Chi Square test). While mammary stem cells were also detected in non-malignant breast lesions, only 41% of the tissues contained ALDH-1 positive cells (p=0.0371, Chi Square test). In patients with BRCA germline mutations ALDH-1 positive cells were more common in p53 positive (p=0.0028, Chi Square test) tumors, in high grade (p=0.0796), and in larger tumors (p=0.0604), while no such association was seen in sporadic cancer cases. In our patients, the expression of ALDH-1 positive cells in breast cancer was neither associated with disease-free and overall survival, nor time to metastasis., Conclusion: Breast cancers from BRCA mutation carriers do not harbor more ALHD-1 positive cells than sporadic tumors, and their more aggressive phenotype can thus not be explained by an increased stem cell pool. The presence of ALDH-1 in normal breast tissue suggests that additional factors determine the biological behavior of mammary stem cells.

Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.