Decrease in treatment intensity predicts worse outcome in patients with locally advanced head and neck squamous cell carcinoma undergoing radiochemotherapy.

PURPOSE: Radiochemotherapy (RCT) is an effective standard therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Nonetheless, toxicity is common, with patients often requiring dose modifications. METHODS: To investigate associations of RCT toxicities according to CTCAE version 5.0 and subsequent therapy modifications with short- and long-term treatment outcomes, we studied all 193 patients with HNSCC who received RCT (70 Gy + platinum agent) at an academic center between 03/2010 and 04/2018. RESULTS: During RCT, 77 (41%, 95% CI 34-49) patients developed at least one ≥ grade 3 toxicity, including seven grade 4 and 3 fatal grade 5 toxicities. The most frequent any-grade toxicities were xerostomia (n = 187), stomatitis (n = 181), dermatitis (n = 174), and leucopenia (n = 98). Eleven patients (6%) had their radiotherapy schedule modified (mean radiotherapy dose reduction = 12 Gy), and 120 patients (64%) had chemotherapy modifications (permanent discontinuation: n = 67, pause: n = 34, dose reduction: n = 7, change to other chemotherapy: n = 10). Objective response rates to RCT were 55% and 88% in patients with and without radiotherapy modifications (p = 0.003), and 84% and 88% in patients with and without chemotherapy modifications (p = 0.468), respectively. Five-year progression-free survival estimates were 20% and 50% in patients with and without radiotherapy modifications (p = < 0.001), and 53% and 40% in patients with and without chemotherapy modifications (p = 0.88), respectively. CONCLUSIONS: Reductions of radiotherapy dose were associated with impaired long-term outcomes, whereas reductions in chemotherapy intensity were not. This suggests that toxicities during RCT should be primarily managed by modifying chemotherapy rather than radiotherapy.

[Jury prize of the Austrian National Prize 2018 : 12 years European Foundation for Quality Management (EFQM) at the University Eye Clinic Graz]. / Jurypreis des Österreichischen Staatspreises 2018 : Zwölf Jahre EFQM (European Foundation for Quality Management) an der Universitäts-Augenklinik Graz.

BACKGROUND: The European Foundation for Quality Management (EFQM) approach has been successfully implemented in healthcare but reports about EFQM awards at university clinics are lacking so far. Can a non-profit organization, such as a university eye department successfully compete with profit companies from industry for the National Prize of the Federal Ministry for Innovation and Business in Austria? MATERIAL AND METHODS: Following successful committed to excellence (C2E) assessments in 2008 and 2010, a 70-page corporate report was compiled strictly according to the EFQM logic (latest version 2013), consisting of basic concepts, criteria matrix and results/approach/deployment/assessment and refinement (RADAR) logic, which formed the basis for an 1­day assessment in 2018. Special emphasis was laid on the development and presentation of the strategy by means of the X­matrix (according to Hoshin-Kanri) between the University Eye Department and its shareholders, the Styrian Hospital Association (KAGes) owned by the Federal State of Styria and the Medical University financed by the Austrian State Federal Ministry. RESULTS: The total points score in the recognized for excellence (R4E) assessment 2018 was 500-550 points, which prompted the jury to award a jury prize of the Austrian National Prize (focus: participative leadership). Potential for improvement, which needs to be worked on in the near future was the alignment of core processes with the main performance indicators of the University Eye Department, which arises from its mission consisting of patient care, research, teaching, training and public relations activities. The development of the strategy with the shareholders has developed from a potential to a strength compared to the R4E assessment from 2017. CONCLUSION: Feedback from the assessor team after the site visit is the greatest added value for a university eye department and/or business enterprise. Improvement measures can be effectively derived following the RADAR logic and lead to a higher quality standard/score and improved performance.

An index with improved diagnostic accuracy for the diagnosis of Crohn's disease derived from the Lennard-Jones criteria.

BACKGROUND: The Lennard-Jones criteria are considered the gold standard for diagnosing Crohn's disease (CD) and include the items granuloma, macroscopic discontinuity, transmural inflammation, fibrosis, lymphoid aggregates and discontinuous inflammation on histology. The criteria have never been subjected to a formal validation process. AIM: To develop a validated and improved diagnostic index based on the items of Lennard-Jones criteria. METHODS: Included were 328 adult patients with long-standing CD (median disease duration 10 years) from three centres and classified as 'established', 'probable' or 'non-CD' by Lennard-Jones criteria at time of diagnosis. Controls were patients with ulcerative colitis (n = 170). The performance of each of the six diagnostic items of Lennard-Jones criteria was modelled by logistic regression and a new index based on stepwise backward selection and cut-offs was developed. The diagnostic value of the new index was analysed by comparing sensitivity, specificity and accuracy vs. Lennard-Jones criteria. RESULTS: By Lennard-Jones criteria 49% (n = 162) of CD patients would have been diagnosed as 'non-CD' at time of diagnosis (sensitivity/specificity/accuracy, 'established' CD: 0.34/0.99/0.67; 'probable' CD: 0.51/0.95/0.73). A new index was derived from granuloma, fibrosis, transmural inflammation and macroscopic discontinuity, but excluded lymphoid aggregates and discontinuous inflammation on histology. Our index provided improved diagnostic accuracy for 'established' and 'probable' CD (sensitivity/specificity/accuracy, 'established' CD: 0.45/1/0.72; 'probable' CD: 0.8/0.85/0.82), including the subgroup isolated colonic CD ('probable' CD, new index: 0.73/0.85/0.79; Lennard-Jones criteria: 0.43/0.95/0.69). CONCLUSION: We developed an index based on items of Lennard-Jones criteria providing improved diagnostic accuracy for the differential diagnosis between CD and UC.

Are endometrial carcinoma cells disseminated at hysteroscopy functionally viable?

OBJECTIVE: The aim of this study was to evaluate the rate of transtubal dissemination of endometrial carcinoma cells by hysteroscopy and the functional viability of disseminated tumor cells by assessing cell adhesion in an in vitro model. METHODS: We studied 24 uteri obtained at TAH+BSO in patients with endometrial carcinoma. Further inclusion criteria were negative peritoneal cytology, no involvement of the uterine serosa or extrauterine disease, and endometrial surface involvement >1 cm in diameter. In vitro fluid hysteroscopy was performed with a 5-mm single-flow rigid hysteroscope. A maximum of 150 ml saline was infused at a maximum pressure of 100 mm Hg for a maximum of 3 min. Fluid running off through the tubes was collected. The cell suspension was enriched by a density gradient centrifugation. The isolated cells had a mean viability of 90% as judged by trypan blue exclusion. Viable cells (5 x 10(4) per 2-cm(2) polyvinyl chloride well plate) were cultured with equal parts of Dulbecco's modified Eagle's minimal essential medium and Ham's F-12 for 24 h. The endpoint of the analysis was the adherence of tumor cells to the polyvinyl chloride well plate, which was taken as a proxy for functional cell viability. Cytological evaluation was performed separately by two cytologists blinded to the source and date of the smears. RESULTS: Transtubal fluid dissemination was seen in 20 of 24 (83%) uteri. Tumor cells were found in 17 specimens (71%). In 10 (42%) specimens the disseminated tumor cells were functionally viable. CONCLUSIONS: Our model suggests that hysteroscopy can cause dissemination of malignant cells into the abdominal cavity from uteri containing endometrial carcinoma and that these cells can be functionally viable and adhere to a matrix.

Association of the vitamin D receptor genotype BB with low bone density in hyperthyroidism.

Bone mineral density (BMD) is modulated by genetic and environmental factors or certain diseases. In several conditions such as low calcium intake, an influence of vitamin D receptor (VDR) polymorphisms on BMD has been suggested. In the present study, we investigated the relationship of Bsm I and Fok I polymorphisms of the VDR gene and BMD in patients with hyperthyroidism, a disease that often results in low BMD. Bsm I and Fok I genotypes were determined in 76 postmenopausal hyperthyroid patients and 62 healthy postmenopausal women as controls. Patients and controls were matched for age, time since menopause, and lifestyle factors and were free of estrogen medication. BMD evaluation included axial dual X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (PQCT). Low BMD was defined as -2.5 STD below the young adult mean value. Biochemical parameters investigated were thyroid hormones, osteocalcin, and 25-(OH)-vitamin D3 as well as routine laboratory data. Low BMD was found in 61% of hyperthyroid patients and in only 23% of euthyroid controls. In the group of hyperthyroid patients with low bone density, the BB genotype (VDR Bsm I polymorphisms) was significantly more frequent (39%) than in controls (13%; p = 0.003) and hyperthyroid patients with normal BMD (6%; p = 0.013). The odds ratio (OR) for low BMD in patients with BB genotype was 5.7 (95% CI, 1.7-19.1; p < 0.005) as compared with the Bb and bb genotypes and 5.5 (95% CI, 2.3-13.2; p < 0.0001) for hyperthyroidism alone. The cumulative risk for low BMD in patients with hyperthyroidism and BB genotype was 31.4 (95% CI, 3.9-256; p < 0.0003). VDR Fok I genotypes showed no significant relationship with BMD or other general or bone-specific parameters. Thus, hyperthyroidism and the genetic background of a BB genotype may promote synergistically the development of low BMD in hyperthyroid patients. Screening for the BB genotype in these patients therefore could help to identify those with particularly high risk for the development of low BMD and allow early treatment.

Course of maternal serum magnesium levels in low-risk gestations and in preterm labor and delivery.

OBJECTIVES: To describe the course of total and ionized magnesium and total calcium levels in maternal serum during low-risk pregnancies and to compare women who developed preterm labor and delivery with those who delivered at term. METHODS: 209 women with low-risk pregnancies were enrolled in a prospective trial before the 18th week of gestation. No woman received oral magnesium supplementation. The ionized and total magnesium and total calcium levels in maternal serum were measured every 4-6 weeks. The data were grouped into 3 gestational periods (/=28 weeks of gestation) for overall comparison and analyzed with the general linear model for repeated measurements and ANOVA. p values of < 0.05 were considered statistically significant. RESULTS: 145 gestations were available for analysis. 27 women were hospitalized for preterm labor and in 16 of these preterm delivery occurred. Ionized and total magnesium and calcium levels were significantly lower after the 18th week of gestation than before. The cation levels in women with preterm labor and delivery did not differ from those with term delivery. CONCLUSION: Ionized and total magnesium and calcium levels decrease with increasing gestational age. Preterm labor and delivery do not seem to be related to changes in serum cation levels.