Exercise oscillatory ventilation in patients with advanced heart failure with and without left ventricular assist device.

BACKGROUND: Exercise oscillatory ventilation (EOV), indicating pathological fluctuations on pulmonary arterial pressure, is associated with mortality in patients with heart failure (HF). Whether left ventricular assist device (LVAD)-induced ventricular unloading can reverse EOV and may prevent short-term rehospitalization has not been investigated. METHODS: We performed a retrospective single-center in- and outpatient analysis of patients with (n = 20, LVAD) and without (n = 27, HF) circulatory support and reduced ejection fraction (EF, 22.8 ± 7.9%). The association of cardiopulmonary exercise testing (CPET) variables and 3 months-rehospitalization (3MR) as a primary outcome was analyzed. Furthermore, CPET variables were compared regarding the presence of EOV (+/-). RESULTS: Lower VO2peak (11.6 ± 4.9 ml/kg/min vs. 14.4 ± 4.3 ml/kg/min, p = 0.039), lower increase of PETCO2 (CI = 0.049-1.127; p = 0.068), and higher VE/VCO2 (43.8 ± 9.5 vs. 38.3 ± 10.6; p = 0.069) were associated with 3MR. Flattening of O2 pulse (CI = 0.139-2.379; p = 0.487) had no impact on 3MR. EOV was present in 59.5% (n = 28/47) of patients, without a significant difference between LVAD and HF patients (p = 0.959). Patients with HF/EOV+ demonstrated significantly lower VO2peak compared with HF/EOV- (p = 0.039). LVAD/EOV+ displayed significantly lower EF (p = 0.004) and fewer aortic valve opening than LVAD/EOV- (p = 0.027). CONCLUSIONS: Lower VO2peak , but not EOV, was associated with 3MR. EOV occurred at a similar rate in LVAD and HF patients, which may illustrate insufficient unloading during exercise in chronic LVAD therapy and may contribute to the limited exercise capacity following LVAD implantation. Simultaneous CPET and right heart catheterization studies are needed to elucidate whether EOV may serve as a non-invasive predictor of insufficient LV unloading necessitating LVAD reprograming.

Early treatment modifications improve chemotherapy adherence in ovarian cancer patients ≥70 years.

OBJECTIVE: Elderly ovarian cancer patients are underrepresented in clinical trials and disadvantaged with regard to therapeutic standards compared to other age groups. We explored the specific performance of a subset of patients aged ≥70 years in a large meta-data set of 3 phase III trials. METHODS: 3333 patients with advanced ovarian cancer recruited into 3 clinical phase III trials of the AGO & GINECO study groups were retrospectively analysed for age-specific prognostic and toxicity parameters. RESULTS: Only 10% (359/3333) of the patients were aged ≥70 years. This subgroup presented with impaired performance statuses (ECOG 2 14.8 vs 10.1%) and higher FIGO-stages (FIGO IIIC-IV 78.5 vs 73.6%) compared to younger patients. Complete operative tumor resection was achieved less frequently (postoperative tumor burden >10 mm 46.7 vs 33.9%) and elderly received less cycles of platinum/taxane-based chemotherapies (>4 cycles 81.9 vs 90.7%). FIGO-stage, histology, postoperative tumor burden and number of chemotherapy cycles were independent prognostic factors in elderly patients. Elderly patients with ≤4 cycles of chemotherapy showed a median OS of 18.4 months compared to 30.9 months in elderly with 5-6 cycles (p < 0.001). This effect was accentuated in elderly patients after complete tumor resection (cumulative survival benefit of 33.8 months). Analyses of chemotherapeutic delivery revealed that elderly patients with at least one cycle delay had higher chances to complete >4 cycles of chemotherapy. CONCLUSIONS: Protocol defined treatment modifications might support completion of >4 cycles of standard chemotherapy in fit elderly OC patients.

The Hypothalamic-Pituitary-Adrenal Axis and Serotonin Metabolism in Individual Brain Nuclei of Mice with Genetic Disruption of the NK1 Receptor Exposed to Acute Stress.

Mice lacking the substance P (SP) neurokinin-1 (NK1) receptor (NK1R-/-mice) were used to investigate whether SP affects serotonin (5-HT) function in the brain and to assess the effects of acute immobilisation stress on the hypothalamic-pituitary-adrenocortical (HPA) axis and 5-HT turnover in individual brain nuclei. Basal HPA activity and the expression of hypothalamic corticotropin-releasing hormone (CRH) in wild-type (WT)- and NK1R-/- mice were identical. Stress-induced increases in plasma ACTH concentration were considerably higher in NK1R-/- mice than in WT mice while corticosterone concentrations were equally elevated in both mouse lines. Acute stress did not alter the expression of CRH. In the dorsal raphe nucleus (DRN), basal 5-HT turnover was increased in NK1R-/- mice and a 15 min stress further magnified 5-HT utilisation in this region. In the frontoparietal cortex, medial prefrontal cortex, central nucleus of amygdala, and the hippocampal CA1 region, stress increased 5-HT and/or 5-hydroxyindoleacetic acid (5-HIAA) concentrations to a similar extent in WT and NK1R-/- mice. 5-HT turnover in the hypothalamic paraventricular nucleus was not affected by stress, but stress induced similar increases in 5-HT and 5-HIAA in the ventromedial and dorsomedial hypothalamic nuclei in WT and NK1R-/- mice. Our findings indicate that NK1 receptor activation suppresses ACTH release during acute stress but does not exert sustained inhibition of the HPA axis. Genetic deletion of the NK1 receptor accelerates 5-HT turnover in DRN under basal and stress conditions. No differences between the responses of serotonergic system to acute stress in WT and NK1R-/- mice occur in forebrain nuclei linked to the regulation of anxiety and neuroendocrine stress responses.

Persistent Full-Thickness Idiopathic Macular Hole: Anatomical and Functional Outcome of Revitrectomy with Autologous Platelet Concentrate or Autologous Whole Blood.

PURPOSE: To evaluate long-term outcome after revitrectomy with autologous platelet concentrate (APC) or whole blood (WB) in persistent idiopathic macular hole (MH) after vitrectomy with internal limiting membrane (ILM) peeling. PROCEDURES: Retrospective study of 75 eyes with persistent MH after vitrectomy with ILM peeling and gas. All patients underwent revitrectomy with gas and APC (n = 61) or WB (n = 14). Main outcome measures were anatomical closure rate and postoperative best-corrected visual acuity (BCVA). RESULTS: Closure rate after revitrectomy was 85.2% (52/61) in the APC group and 7.1% (1/14) in the WB group. Median follow-up was 58 (range 3-147) months. Median BCVA (logMAR) in patients with finally closed MHs was 0.4 ± 0.3. Patients with defects of the ellipsoid zone had significantly worse postoperative BCVA. Morphological MH configuration (atrophic or elevated edges) did not correlate with final closure rate. CONCLUSIONS: Revitrectomy with APC and gas is a very effective treatment in persistent MH after vitrectomy with ILM peeling and gas.

Fertility after recurrent miscarriages: results of an observational cohort study.

PURPOSE: Recurrent pregnancy losses (RPL) are considered a pathological condition associated with heterogeneous laboratory and clinical findings, and are also linked to subfertility. We attempt to rank parameters derived from past history and diagnostic results with regard to the prognosis. METHODS: Observational trial on 719 consecutive couples who were referred to a tertiary immunological care centre (2006-2014) after three or more primary miscarriages. Information on past obstetric history and diagnostic procedures at baseline were correlated with cumulative pregnancy and delivery rates using Kaplan-Meier estimation, logistic regression and multivariate analysis. RESULTS: At baseline, median female age was 34.1 years, waiting time 3 years (1-17), number of preceding miscarriages 3 (3-9), 147 women (20.4%) had conceived at least once in ART or AIH cycles. After a median follow-up of 33.7 (1.7-123.0) months, 5-year pregnancy and delivery rates were 86.1 and 64.5%. Female age (< 35 years), waiting time (< 3 years) until baseline, tubal competence, and male factor fertility significantly correlated with favourable outcome (p < 0.001), while body mass index (> 29 kg/m2), number of preceding miscarriages (> 4), late miscarriages, preclinical losses and smoking revealed non-significant negative trends. Mode of conception until baseline (spontaneously or ART/AIH) and classification into idiopathic and non-idiopathic RPL showed no prognostic relevance. CONCLUSION: Although in general, chances to conceive a child are retained after three or more miscarriages, factors related to subfertility of both partners have an important impact on the outcome. Therefore, prolonged time to pregnancy (> 6-9 months) should result in preventive gynaecological care from the first miscarriage on, so that fertility can be preserved as best as possible.

Correction to: Two-year outcome after recurrent implantation failure: prognostic factors and additional interventions.

The article Two-year outcome after recurrent implantation failure: prognostic factors and additional interventions.

In situ localization of tumor cells associated with the epithelial-mesenchymal transition marker Snail and the prognostic impact of lymphocytes in the tumor microenvironment in invasive ductal breast cancer.

PURPOSE: Tumor surgery is aimed at complete resection of the lesion while ensuring a sufficient tumor-specific safety distance. Nevertheless, in many cases the most peripheral part - the invasion front - remains in situ. Tumor cells at the tumor margin have been reported to lose their epithelial properties and acquire features of mesenchymal cells. The process of epithelial-to-mesenchymal transition (EMT) is believed to be of prime importance for tissue and vessel invasion. Furthermore, the detection of tumor-infiltrating lymphocytes in the microenvironment of breast cancer might serve as a reliable prognostic marker. METHODS: We investigated tissue microarrays of 352 breast cancer patients with regard to the presence and distribution of the EMT factor Snail, and the presence of FoxP3, CD3 and CD8 in the immune microenvironment. RESULTS: The expression of the transcription factor Snail is strongly associated with longer disease-free and overall survival. The presence of CD3, CD8 or FoxP3 is associated with a better outcome, although statistically significant results were noted only for FoxP3. The prognostic significance of FoxP3 and Snail were also proven in multivariate analysis. CONCLUSIONS: Based on previous studies concerning the intratumoral heterogeneity of EMT, our results suggest that Snail and FoxP3 are possible prognostic markers for breast cancer. The diverse presence of lymphocytes in the tumor microenvironment (CD3 and CD8) was confirmed. Although the importance of these markers is known, their specific role in tumor invasion and metastasis as well as their hierarchical organization in these tumors remain unclear.

Thinning of Inner Retinal Layers after Vitrectomy with Silicone Oil versus Gas Endotamponade in Eyes with Macula-Off Retinal Detachment.

PURPOSE: To evaluate retinal layer thickness with optical coherence tomography (OCT) in eyes with macula-off retinal detachment after silicone oil (SiO) or gas endotamponade. PROCEDURES: Cross-sectional study of 40 eyes with macula-off rhegmatogenous retinal detachment that underwent vitrectomy. 20 eyes received SiO tamponade and 20 matched eyes received gas. 33 healthy fellow eyes served as controls. Macular spectral domain OCT was performed with automated layer detection in the 5 inner subfields of the Early Treatment Diabetic Retinopathy Study (ETDRS) map. RESULTS: Comparing the SiO group with the gas group, the ganglion cell layer showed a significant thinning in all fields of the inner ring of the ETDRS map, the inner plexiform layer in the nasal, superior and temporal quadrants, and the outer plexiform layer in the nasal quadrant. CONCLUSIONS: Inner retinal layers in the fovea/parafovea were significantly thinner in the SiO group. Prospective studies are warranted to further elucidate possible retinal adverse effects of SiO tamponade.

An In Vitro Study of Condylar Displacement Caused by Interocclusal Records: Influence of Recording Material, Storage Time, and Recording Technique.

PURPOSE: To evaluate the condylar displacement after mounting working casts using different interocclusal recording materials and to analyze the influence of the storage time and the recording technique on the displacement caused by the interocclusal record. MATERIALS AND METHODS: Eight interocclusal records were made in each of the following groups: G1: Aluwax (aluminum wax), G2: Beauty Pink wax (hydrocarbon wax compound), G3: Futar D Fast, G4: Futar Scan (G3, G4: vinylpolysiloxane), G5: Ramitec (polyether), G6: LuxaBite (composite resin based on bis-acryl), G7: LuxaBite corrected with Aluwax. A condylar-positioning indicator measured the condylar displacement in the three planes after storage of the records for two periods of 1 and 48 hours. Two-way ANOVA was used to determine the influences of recording materials and each of the following factors: (1) region (record and non-record side), (2) storage time, and (3) recording technique. The statistical significance level was set at p < 0.05. RESULTS: The vertical displacement caused by the interocclusal records in the record side after storage time of 1 hour ranged between 0.29 mm (Aluwax) and 0.14 mm (Futar Scan). The lateral displacement ranged between 0.13 mm (Aluwax) and 0.02 mm (Ramitec) while the anteroposterior displacement ranged between 0.15 mm (Ramitec) and 0.04 mm (Futar Scan). The corrected resin record showed generally lower displacement values than other materials tested (0.03, 0.02, and 0.07, respectively). On the non-record side, the values were lower than that on the record side. The condylar displacement increased after a storage time of 48 hours for all materials. Both factors, storage time and recording technique, had statistically significant influence on the condylar displacement. CONCLUSIONS: Based on the results, the vertical displacement of the condyle caused by the interocclusal records was higher than the lateral or the anteroposterior displacement. Elastomers caused statistically significantly less condylar displacement than waxes or uncorrected composite resin. Corrected LuxaBite records with Aluwax showed significantly less condylar displacement than all other materials.

Two-year outcome after recurrent first trimester miscarriages: prognostic value of the past obstetric history.

PURPOSE: Recurrent miscarriage (RM) is a stressful condition which gives rise to extensive diagnostic evaluation and is seen as a potentially curable maternal disease. Nevertheless, epidemiological data have shown that outcome is related to fertility. In addition to maternal age and number of preceding miscarriages, further markers derived from the past history may support counselling. METHODS: Observational trial comprising 228 couples who were referred between 1996 and 2003 for immunological evaluation at maternal ages 20-39 years after three or more spontaneously conceived primary first trimester miscarriages. They were interviewed in 2005, ongoing pregnancies were followed up until birth in 2006. Past obstetric history was correlated with 2 year cumulative pregnancy and delivery rates (CPR, CDR). RESULTS: CPR and CDR were 206/228 (90.4 %) and 174/228 (76.4 %). Duration of infertility was associated with lower CPR (up to 3/>3 years, p < 0.01), whereas age and number of preceding losses inversely correlated with CDR (<35 years/35-39 years, p < 0.002; 3/>3 miscarriages, p < 0.002). Detection of an embryonic heart beat in 2-3 of the first three miscarriages resulted in favourable outcome (CPR: p < 0.02, CDR: p < 0.002). Prognosis was excellent in younger fertile women after three miscarriages where vital signs had been detected; under less favourable conditions not only risks for further miscarriage, but also for secondary infertility were elevated. CONCLUSION: Secondary infertility is a feature of RM. Embryonic vital signs in preceding pregnancies are prognostic markers and should be regarded as a strong confounding factor in trials on therapeutic interventions. Prevention may be more appropriate than treatment.

Soluble receptor for advanced glycation end products as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects.

INTRODUCTION: Obesity is associated with low-grade systemic inflammation which is thought to trigger the development of comorbidities such as type 2 diabetes. The soluble receptor for advanced glycation end products (sRAGE) belongs to the innate immune system and has been linked to obesity, recently. The aim of the present study was to examine whether serum sRAGE concentrations are related to the grade of weight loss and improvement of insulin resistance due to a very low calorie diet (VLCD). METHODS: 22 severe obese subjects (Median Body Mass Index (BMI): 44.5kg/m(2)) were included in a dietary intervention study of 6month, consisting of a very low calorie formula diet phase (VLCD: 800kcal/d) for 12 weeks and a following 12 week weight maintenance phase. Fasting glucose, fasting insulin, adiponectin, leptin and sRAGE were determined from sera. Insulin sensitivity was estimated by Homeostasis Model Assessment (HOMA) index and leptin-to-adiponectin-ratio (LAR). RESULTS: Mean body weight reduction by VLCD accounted to 21.7kg with a significant improvement of insulin resistance. At baseline, sRAGE serum levels were significantly inversely related to BMI (rS=-0.642, p=0.001) and HOMA (rS=-0.419, p=0.041). Of interest, sRAGE serum levels at baseline were significantly lower in study subjects with greater reduction of BMI (p=0.017). In addition, a significantly greater HOMA reduction was observed in subjects with lower sRAGE serum levels at baseline (p=0.006). Finally, correlation analysis revealed, that changes of sRAGE serum levels were significantly correlated to changes of BMI (rS=-0.650, p=0.022) during intervention. CONCLUSION: Anti-inflammatory sRAGE might be a potential future biomarker to predict weight loss and improvement of insulin resistance by a VLCD whereby lower baseline sRAGE serum levels indicate a better outcome of the dietary intervention.

Malassezia spp.-specific immunoglobulin E level is a marker for severity of atopic dermatitis in adults.

The significance of allergen-specific IgE as marker for severity of atopic dermatitis is controversial. The aim of this study was to determine the frequency of IgE-mediated sensitisation to food and environmental allergens in 132 children and 67 adults with atopic dermatitis, and its correlation to severity of atopic dermatitis (SCORAD). Total IgE was elevated (> 100 kU/l) in 79.7% of adults and 46.8% of children. Sensitisation frequencies to allergens, particularly microbial allergens, were up to 10-fold higher in adults compared to children. Severity of atopic dermatitis correlated with elevated total IgE in adults (r = 0.549, p < 0.001) and children (r = 0.344, p = 0.005) and with Malassezia spp.-specific IgE in adults (r = 0.429, p = 0.007). Total IgE is a marker for severe atopic dermatitis in both age groups. Malassezia spp.-specific IgE is an important allergen-specific marker for severity of atopic dermatitis in adults.

Comparison of a continuous noninvasive arterial pressure device with invasive measurements in cardiovascular postsurgical intensive care patients: a prospective observational study.

BACKGROUND: Arterial pressure monitoring using the a continuous noninvasive arterial pressure (CNAP) device during general anaesthesia is known to be interchangeable with continuous invasive arterial pressure (CIAP) monitoring. Agreement with invasive measurements in cardiovascular postsurgical intensive care patients has not been assessed. OBJECTIVE: The objective of this study is to assess the agreement and interchangeability of CNAP with CIAP in cardiovascular postsurgical patients and to determine the effects of cardiac arrhythmia, catecholamine dosage, respiratory weaning and calibration intervals on agreement. DESIGN: A prospective observational study. SETTING: German university hospital cardiovascular ICU. Data were collected from April 2010 to December 2011. PATIENTS: From 110 enrolled patients, 104 were included. Inclusion criteria were American Society of Anaesthesiologists (ASA) physical status III or IV patients undergoing controlled ventilation. Exclusion criteria included emergencies, complete heart block and marked arterial pressure differences greater than 10 mmHg in the two arms. MAIN OUTCOME MEASURES: Bland-Altman plots, bias, precision, 95% limits of agreement, percentage error and agreement : tolerability indexes (ATIs) were estimated to determine clinical agreement. RESULTS: From 11 222 arterial pressure readings, biases (SD) for CIAP-CNAP for systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and mean arterial pressure (MAP) for all patients were 4.3 (11.6), -9.4 (8) and -6 (7.6) mmHg, respectively. Cardiac arrhythmia (4.1 (13.1), -14.4 (8.3), -9.5 (8.9) mmHg) and long interval to last calibration [4.5 (15), -9.8 (9.5), -6.4 (9.1) mmHg] impaired the accuracy of CNAP with failed interchangeability criteria defined by the percentage error. In contrast, use of catecholamines (epinephrine or norepinephrine infusions >0.1 µg kg min), short calibration intervals and weaning conditions did not affect accuracy, interchangeability and agreement, especially of MAP. Agreement was defined as acceptable for MAP for all data and subgroups (ATI 0.8 to 1.0) and at worst, marginal for SAP and DAP (ATI 0.9 to 1.6). CONCLUSION: CNAP showed acceptable agreement defined by the ATI with invasive measurements for MAP and partially for DAP, but there was considerable variability for SAP. MAP should be preferred for clinical decision making. Cardiac arrhythmia, in contrast to catecholamine dosage or weaning procedures, impaired the accuracy, agreement and interchangeability of CNAP. TRIAL REGISTRATION: Clinical trials.gov identifier NCT01003665.

The role of the antileukoprotease SLPI in smoking-induced human papillomavirus-independent head and neck squamous cell carcinomas.

Recently, we showed that increased SLPI levels prevent human papillomavirus (HPV) infections and metastasis in smoking-induced, non-HPV-driven head and neck squamous cell carcinoma (HNSCC). Here, we focus on the role of SLPI in non-HPV-driven HNSCC, investigating tumor tissue and non-neoplastic mucosa from the same patients and from non-HNSCC patients. Gene and protein expression of SLPI and gene expression of annexin 2 (a SLPI receptor), nicotine receptor (α7AChR) and arylhydrocarbon receptor (AhR) were analyzed in HNSCC patients (20 smokers; 16 nonsmokers). SLPI-results were correlated with the patients' HPV status. Non-neoplastic mucosa of HNSCC patients and normal mucosa from non-HNSCC individuals (18 smokers; 20 nonsmokers) was analyzed for the same parameters. Tissue of the inferior turbinate (n = 10) was incubated with nicotine for analysis of the same genes. SLPI gene expression in tumor tissue was 109.26 ± 23.08 times higher in smokers versus nonsmokers. Non-neoplastic mucosa of smokers showed also higher SLPI gene expression (10.49 ± 1.89-fold non-HNSCC; 18.02 ± 3.93-fold HNSCC patients). Annexin 2 gene expression was also increased in smokers. SLPI data were corroborated by immunohistochemistry. A nicotine dependent correlation between SLPI and annexin 2 gene expression (r(2) = 0.15, p < 0.001) was shown ex vivo. Nicotine and smoking increased α7AChR and AhR gene expression. Five patients, showing no/low SLPI expression, were HPV16-positive. A significant correlation between smoking and SLPI expression in tumors and to our knowledge for the first time in mucosa of HNSCC and non-HNSCC patients was established. Together with the finding that all patients with HPV infection showed no/low SLPI expression, these data support our intriguing hypothesis that smoking induced upregulated SLPI prevents HPV infections.

Effect of deproteinized bovine bone matrix coverage on the resorption of iliac cortico-spongeous bone grafts - a prospective study of two cohorts.

OBJECTIVES: The augmentation of the alveolar ridge using iliac cortico-spongeous bone grafts is routinely used. However, bone grafts show a substantial degree of resorption, which may negatively affect the long-term success of dental implants in the augmented area. The aim of this study was to evaluate the effect of a deproteinized bovine bone matrix coverage on the resorption of iliac bone grafts. MATERIAL AND METHODS: Two cohorts consisting of 40 patients who received a vertical augmentation of the alveolar ridge with onlay grafts from the iliac crest were prospectively investigated over a period of 2 years. In half of the patients (n = 40), the grafts were covered by a thin layer of deproteinized bovine bone matrix (DBBM cohort). The other 40 patients received the identical surgical procedure without a DBBM coverage (non-DBBM cohort). The graft height/resorption was radiographically determined immediately after surgery, 6 months, 1 year, and 2 years postoperatively. RESULTS: The height of the bone graft 6 months after surgery accounted 92.15% of the initial value in the DBBM cohort and 87.76% in the non-DBBM cohort. One year after augmentation, the height reduced to 83.95% in the DBBM cohort and 72.92% in the non-DBBM cohort. Two years after surgery, the resorption slowed down and the height of the grafts accounted 81.27% in the DBBM cohort and 71.43% in the non-DBBM cohort. The difference was statistically significant. CONCLUSION: Deproteinized bovine bone matrix reduces the postoperative resorption of iliac bone block grafts and may therefore enhance the long-term implant prognosis in the augmented area.

Investigation of a matrix sentence test in noise: reproducibility and discrimination function in cochlear implant patients.

OBJECTIVE: The aim of this study was to describe common properties (reproducibility, discrimination function, and its steepness) of matrix tests used for cochlear implant (CI) users and to obtain data for the German-language version matrix test, the Oldenburg sentence test (OLSA), presented in noise. DESIGN: The speech reception thresholds (SRT) in noise were measured by means of an adaptive test procedure, and by measurement at various signal-to-noise ratios to determine the course of the entire discrimination function per subject. STUDY SAMPLE: The measurements were performed on 38 CI users fitted with a Cochlear(™) Freedom(®) or a Cochlear(™) Nucleus(®) 5 CI system. RESULTS: The test-retest reproducibility showed a significant dependence on the SRT in noise. For the better performers, the test-retest difference was found to be smaller, while for the poorer performers the difference increased. For the better performers, the slope of the discrimination function at SRT (s50) was comparable to that for individuals with normal hearing, while for the poorer performers the s50 tended to be significantly reduced. CONCLUSIONS: As the CI users differed significantly in their SRT and their s50, a unified discrimination function for CI users must not be used. Further tailoring of the procedure may be required, especially for poorer CI performers.

Differential expression and in vivo secretion of the antimicrobial peptides psoriasin (S100A7), RNase 7, human beta-defensin-2 and -3 in healthy human skin.

Antimicrobial peptides (AMP) are key players in the skin's defense system. Previous observations suggest a site- and age-dependent expression of individual AMP. We investigated the expression and secretion patterns of four important AMP in a representative collective of healthy human skin samples. Levels of psoriasin, RNase 7 and hBD-3 expression - assessed by immunohistochemistry - varied between different body localisations. Older individuals expressed hBD-2 more frequently. No gender-related expression was observed. The in vivo secretion of psoriasin, measured in skin washing fluids using ELISA, was related to body localisation and age, whereas RNase 7 secretion showed no significant differences regarding these variables. HBD-2 and -3 secretion could not be detected. Our findings suggest the usage of control samples matching localisation and approximate age (in the case of hBD-2) for comparative immunohistochemical analysis. To avoid bias through great interindividual differences, sufficient large collectives should be used for in vivo secretion analyses.

Comparison of platelet rich fibrin and collagen as osteoblast-seeded scaffolds for bone tissue engineering applications.

OBJECTIVES: The loss of jaw bone caused by different kinds of pathologies leads to dysfunction and reduced quality of life in affected patients. Thus, the pivotal goal in bone tissue engineering is to reconstruct these defects. The essential precondition for new tissue generation is an extracellular matrix which acts as a scaffold so that cells can migrate, differentiate, and proliferate. Fibrin, a biopolymer responsible for blood clot formation, has been shown to be suitable for tissue engineering applications. The aim of the present study is a comparison of platelet rich fibrin (PRF) with the commonly used collagen membrane BioGide(®) as a scaffold for human osteoblast cell seeding for bone tissue engineering. MATERIAL AND METHODS: Human osteoblasts were cultured with eluates from PRF (n = 7) and BioGide(®) (n = 8) membranes incubated in serum-free cell culture medium. Vitality of these cells was assessed by fluorescein diacetate and propidium iodide staining, biocompatibility with the lactate dehydrogenase test and proliferation levels with the MTT ([3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide]), and BrdU (5-bromo-2-deoxyuridine) tests. In addition, human osteoblasts were seeded on both membrane systems and cell growth was compared by the water soluble tetrazolium (WST-1) (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate) test and scanning electron microscopy (SEM). Osteoblastic differentiation was assessed by alkaline phosphatase activity measured by ELISA in the supernatant of osteoblasts cultivated on PRF membranes (n = 10), PRF clots (n = 10), and BioGide(®) membranes (n = 10). RESULTS: Lactate dehydrogenase test values were higher for PRF compared to BioGide(®) . The BrdU test showed superior cell growth after cultivation in eluate from PRF than in eluate from BioGide(®) . The WST-1 assay demonstrated superior cell proliferation on PRF than on BioGide(®) . SEM revealed osteoblast colonization of both membranes. Cultivation of osteoblasts on PRF membranes and PRF clots showed significantly higher alkaline phosphatase activity than on BioGide(®) membranes. CONCLUSION: Metabolic activity and proliferation of human osteoblast cells in vitro were supported to a significant higher extent by eluates from PRF membranes. Both membranes are suitable as scaffolds for cultivation of human osteoblast cells in vitro; proliferation was significant higher on PRF membranes and on PRF clot than on BioGide(®) membranes.

Combined surgical and hormone therapy for endometriosis is the most effective treatment: prospective, randomized, controlled trial.

STUDY OBJECTIVE: To evaluate 3 therapy strategies: hormone therapy, surgery, and combined treatment. DESIGN: Prospective, randomized, controlled study (Canadian Task Force classification I). SETTING: University-based teaching hospital. PATIENTS: Four hundred fifty patients with genital endometriosis, aged 18 to 44 years, before first laparoscopy. INTERVENTIONS: Patients were randomly assigned to 1 of 3 treatment groups: hormone therapy, surgery, or combined treatment. Patients were reevaluated at second-look laparoscopy, at 2 to 2 months after 3-month hormone therapy in groups 1 and 3 and at 5 to 6 months in group 2 (surgical treatment alone). Outcome data were focussed on the endometriosis stage, recurrence of symptoms, and pregnancy rate. MEASUREMENTS AND MAIN RESULTS: All treatment options, independent of the initial Endoscopic Endometriosis Classification stage, achieved an overall cure rate of ≥50%. A cure rate of 60% was achieved with the combined treatment, 55% with exclusively hormone therapy, and 50% with exclusively surgical treatment. Recurrence of symptoms was lowest in patients who received combined treatment. Significant benefit was achieved for dysmenorrhea and dyspareunia. An overall pregnancy rate of 55% to 65% was achieved, with no significant difference between the therapeutic options. CONCLUSION: In the quest to find the most effective treatment of genital endometriosis, this clinical randomized study shows the lowest incidence of recurrence with combined surgical and medical treatment and improved pregnancy rate in any medically treated patients with or without surgery. The highest cure rate (Endoscopic Endometriosis Classification stage 0) for endometriosis was also achieved in the combined treatment group.

Influence of a guideline or an additional rapid strep test on antibiotic prescriptions for sore throat: the cluster randomized controlled trial of HALS (Hals und Antibiotika Leitlinien Strategien).

BACKGROUND: Pharyngitis due to Group A beta-hemolytic streptococci (GAS) is seen as the main indication for antibiotics for sore throat. In primary care settings prescription rates are much higher than the prevalence of GAS. Recommendations in international guidelines differ considerably. A German guideline suggested to consider antibiotics for patients with Centor or McIsaac scores ≥ 3, first choice being penicillin V for 7 days, and recommended analgesics for all. We investigated, if the implementation of this guideline lowers the antibiotic prescription rate, and if a rapid antigen detection strep-test (RADT) in patients with scores ≥ 3 lowers the rate further. METHODS: HALS was an open pragmatic parallel group three-arm cluster-randomized controlled trial. Primary care practices in Northern Germany were randomized into three groups: Guideline (GL-group), modified guideline with a RADT for scores ≥ 3 (GL-RADT-group) or usual care (UC-group). All practices were visited and instructed by the study team (outreach visits) and supplied with material according to their group. The practices were asked to recruit 11 consecutive patients ≥ 2 years with an acute sore throat and being at least moderately impaired. A study throat swab for GAS was taken in every patient. The antibiotic prescription rate at the first consultation was the primary outcome. RESULTS: From October 2010 to March 2012, 68 general practitioners in 61 practices recruited 520 patients, 516 could be analyzed for the primary endpoint. Antibiotic prescription rates did not differ between groups (p = 0.162) and were about three times higher than the GAS rate: GL-group 97/187 patients (52%; GAS = 16%), GL-RADT-group 74/172 (43%; GAS = 16%) and UC-group 68/157 (43%; GAS = 14%). In the GL-RADT-group 55% of patients had scores ≥ 3 compared to 35% in GL-group (p < 0.001). After adjustment, in the GL-RADT-group the OR was 0.23 for getting an antibiotic compared to the GL-group (p = 0.010), even though 35 of 90 patients with a negative Strep-test got an antibiotic in the GL-RADT-group. The prescription rates per practice covered the full range from 0 to 100% in all groups. CONCLUSION: The scores proposed in the implemented guideline seem inappropriate to lower antibiotic prescriptions for sore throat, but better adherence of practitioners to negative RADTs should lead to fewer prescriptions. TRIAL REGISTRATION: DRKS00013018, retrospectively registered 28.11.2017.