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.

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.

A Continuous Correlation Between Residual Tumor Volume and Survival Recommends Maximal Safe Resection in Glioblastoma Patients: A Nomogram for Clinical Decision Making and Reference for Non-Randomized Trials.

OBJECTIVE: The exact role of the extent of resection or residual tumor volume on overall survival in glioblastoma patients is still controversial. Our aim was to create a statistical model showing the association between resection extent/residual tumor volume and overall survival and to provide a nomogram that can assess the survival benefit of individual patients and serve as a reference for non-randomized studies. METHODS: In this retrospective multicenter cohort study, we used the non-parametric Cox regression and the parametric log-logistic accelerated failure time model in patients with glioblastoma. On 303 patients (training set), we developed a model to evaluate the effect of the extent of resection/residual tumor volume on overall survival and created a score to estimate individual overall survival. The stability of the model was validated by 20-fold cross-validation and predictive accuracy by an external cohort of 253 patients (validation set). RESULTS: We found a continuous relationship between extent of resection or residual tumor volume and overall survival. Our final accelerated failure time model (pseudo R2 = 0.423; C-index = 0.749) included residual tumor volume, age, O6-methylguanine-DNA-methyltransferase methylation, therapy modality, resectability, and ventricular wall infiltration as independent predictors of overall survival. Based on these factors, we developed a nomogram for assessing the survival of individual patients that showed a median absolute predictive error of 2.78 (mean: 1.83) months, an improvement of about 40% compared with the most promising established models. CONCLUSIONS: A continuous relationship between residual tumor volume and overall survival supports the concept of maximum safe resection. Due to the low absolute predictive error and the consideration of uneven distributions of covariates, this model is suitable for clinical decision making and helps to evaluate the results of non-randomized studies.

Vital capacity and valvular dysfunction could serve as non-invasive predictors to screen for exercise pulmonary hypertension in the elderly based on a new diagnostic score.

Introduction: Exercise pulmonary hypertension (exPH) has been defined as total pulmonary resistance (TPR) >3 mm Hg/L/min and mean pulmonary artery pressure (mPAP) >30 mm Hg, albeit with a considerable risk of false positives in elderly patients with lower cardiac output during exercise. Methods: We retrospectively analysed patients with unclear dyspnea receiving right heart catheterisation at rest and exercise (n=244) between January 2015 and January 2020. Lung function testing, blood gas analysis, and echocardiography were performed. We elaborated a combinatorial score to advance the current definition of exPH in an elderly population (mean age 67.0 years±11.9). A stepwise regression model was calculated to non-invasively predict exPH. Results: Analysis of variables across the achieved peak power allowed the creation of a model for defining exPH, where three out of four criteria needed to be fulfilled: Peak power ≤100 Watt, pulmonary capillary wedge pressure ≥18 mm Hg, pulmonary vascular resistance >3 Wood Units, and mPAP ≥35 mm Hg. The new scoring model resulted in a lower number of exPH diagnoses than the current suggestion (63.1% vs. 78.3%). We present a combinatorial model with vital capacity (VCmax) and valvular dysfunction to predict exPH (sensitivity 93.2%; specificity 44.2%, area under the curve 0.73) based on our suggested criteria. The odds of the presence of exPH were 2.1 for a 1 l loss in VCmax and 3.6 for having valvular dysfunction. Conclusion: We advance a revised definition of exPH in elderly patients in order to overcome current limitations. We establish a new non-invasive approach to predict exPH by assessing VCmax and valvular dysfunction for early risk stratification in elderly patients.

The Feasibility of High-Intensity Interval Training in Patients with Intensive Care Unit-Acquired Weakness Syndrome Following Long-Term Invasive Ventilation.

BACKGROUND: Intensive care unit-acquired weakness syndrome (ICUAWS) can be a consequence of long-term mechanical ventilation. Despite recommendations of early patient mobilisation, little is known about the feasibility, safety and benefit of interval training in early rehabilitation facilities (ERF) after long-term invasive ventilation. METHODS AND RESULTS: We retrospectively analysed two established training protocols of bicycle ergometry in ERF patients after long-term (> 7 days) invasive ventilation (n = 46). Patients conducted moderate continuous (MCT, n = 24, mean age 70.3 ± 10.1 years) or high-intensity interval training (HIIT, n = 22, mean age 63.6 ± 12.6 years). The intensity of training was monitored with the BORG CR10 scale (intense phases ≥ 7/10 and moderate phases ≤ 4/10 points). The primary outcome was improvement (∆-values) of six-minute-walk-test (6 MWT), while the secondary outcomes were improvement of vital capacity (VCmax), forced expiratory volume in 1 s (FEV1), maximal inspiratory pressure (PImax) and functional capabilities (functional independence assessment measure, FIM/FAM and Barthel scores) after 3 weeks of training. No adverse events were observed. There was a trend towards a greater improvement of 6 MWT in HIIT than MCT (159.5 ± 64.9 m vs. 120.4 ± 60.4 m; p = .057), despite more days of invasive ventilation (39.6 ± 16.8 days vs. 26.8 ± 16.2 days; p = .009). VCmax (∆0.5l ± 0.6 vs. ∆0.5l ± 0.3; p = .462), FEV1 (∆0.2l ± 0.3 vs. ∆0.3l ± 0.2; p = .218) PImax (∆0.8 ± 1.1 kPa vs. ∆0.7 ± 1.3pts; p = .918) and functional status (FIM/FAM: ∆29.0 ± 14.8pts vs. ∆30.9 ± 16.0pts; p = .707; Barthel: ∆28.9 ± 16.0 pts vs. ∆25.0 ± 10.5pts; p = .341) improved in HIIT and MCT. CONCLUSIONS: We demonstrate the feasibility and safety of HIIT in the early rehabilitation of ICUAWS patients. Larger trials are necessary to find adequate dosage of HIIT in ICUAWS patients.

Prediction of pulmonary hypertension in older adults based on vital capacity and systolic pulmonary artery pressure.

OBJECTIVE: Right heart catheterization (RHC) is associated with a higher procedural risk in older adults, but non-invasive estimation of pulmonary hypertension (PH) is a challenge. We aimed to elaborate a non-invasive prediction model to estimate PH. METHODS AND DESIGN: We retrospectively analysed 134 older adults (70.0 years ±12.3; 44.9% males) who reported to our clinic with unclear dyspnea between 01/2015 and 01/2020 and had received RHC as a part of their diagnostic workup. Lung function testing, analysis of blood gas samples, 6 min walk distance and echocardiography were performed within 24 hours of RHC. MAIN OUTCOME MEASURES: In a stepwise statistical approach by using an in/exclusion algorithm (using the AIC criterion) we analysed non-invasive parameters to test their value in predicting PH (defined as mean pulmonary artery pressure, PAmean, >25mmHg). Discrimination capability of the final model was measured by the AUC (area under curve) from an ROC (receiver operating characteristics) analysis. RESULTS: We yielded a sensitivity of 87.2% and a specificity of 62.5% in a combinatorial logistical model with systolic pulmonary artery pressure (sPAP) and forced vital capacity (VCmax), the discrimination index was 86.7%. The odds ratios for an increase of 10 mmHg of sPAP were 2.99 (2.08-4.65) and 1.86 (1.11-3.21) for a 1 l decrease in VCmax. On their own, VCmax proved to be specific (83.3%), while sPAP was a sensitive (79.1%) predictor for PH. CONCLUSIONS: We provide a combinatorial model to predict PH from sPAP and VCmax in older adults, which may help to avoid invasive procedures.

Determinants of Left Ventricular Dysfunction and Remodeling in Patients With Corrected Tetralogy of Fallot.

Background The aim of this study was to identify in asymptomatic patients with repaired tetralogy of Fallot the prevalence and determinants of impaired left-sided cardiac function and adverse ventricular remodeling and the relation of left ventricular (LV) dysfunction and remodeling with cardiopulmonary exercise capacity. Methods and Results In a cross-sectional study, 103 patients with tetralogy of Fallot (median age, 16.3 years) in New York Heart Association class 1, with surgical repair at a median age of 1.1 years, and 63 age-matched controls were studied. LV, right ventricular function and geometry, LV myocardial extracellular volume (n=57), and left atrial function were quantified with cardiac magnetic resonance. Peak oxygen consumption was measured by a standardized cardiopulmonary exercise test (n=70). Patients with tetralogy of Fallot had lower LV ejection fraction (P=0.001; 49% below age-adjusted fifth percentile for controls), lower LV mass index (P=0.003), lower LV mass/volume ratio (P<0.01), and impaired left atrial function. Right ventricular mass/volume ratio was the best predictor for LV systolic dysfunction and for a lower LV mass/volume ratio. Compared with controls, LV extracellular volume was higher (P<0.001), particularly in female patients, and associated with subnormal peak oxygen consumption (P=0.037). A peak oxygen consumption below the third percentile reference level was more likely with decreasing LV ejection fraction (P=0.008), and lower LV mass index (P=0.024), but independent of right ventricular ejection fraction. Conclusions In New York Heart Association class 1 patients with tetralogy of Fallot, frequent impaired systolic and diastolic LV function, LV adverse remodeling with LV atrophy, a decreased mass/volume ratio, and extracellular matrix expansion suggest cardiomyopathic changes. The best predictor for LV systolic dysfunction was the right ventricular mass/volume ratio. The subnormal peak oxygen consumption indicates that monitoring of LV status may be important for long-term prognosis.

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.

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.

Transoral Laser Microsurgery for Supraglottic Cancer.

INTRODUCTION: Transoral laser microsurgery (TLM) is an accepted and effective treatment strategy for supraglottic carcinomas. Early supraglottic carcinoma has excellent outcomes independently of the treatment approach. The role of TLM for the treatment of locally advanced tumors is debated. Particularly, the functional outcomes after TLM have to be proven by functional assessment of large cohorts of patients. This study analyzes the oncologic and functional outcomes after TLM for supraglottic carcinomas. PATIENTS AND METHODS: Ninety-one patients with pT1-pT4a supraglottic carcinomas treated between January 2002 and December 2012 were analyzed. Distribution of tumors (UICC 2010) was 11 patients with pT1, 31 patients with pT2, 36 patients with pT3, and 13 patients with pT4a tumors. Node status was positive in 40 (43.6%) patients; 61 (67.1%) patients had stage III or IVa disease. Local control and survival were estimated using the Kaplan-Meier method. For the assessment of functional outcomes, the MD Anderson Dysphagia Inventory (MDADI), the Voice Handicap Index-10 (VHI-10), and the performance status scale for head and neck cancer [Performance Status Scale for Head and Neck (PSS-HN)] were used. RESULTS: The median age was 62 years (range, 33-88 years). Fourteen (15.4%) patients developed a local or locoregional recurrence. The 5-year local control rate and 5-year ultimate local control rate were 72 and 92%, respectively. The 5-year overall survival rate was 63%. Twelve (13.2%) patients needed temporary tracheostomy. Sixty-eight (74.0%) patients had a nasogastric feeding tube post-operatively. At 1-year post-operative follow-up, only three patients were PEG dependent. The median VHI-10 score was 35, the median MDADI composite score was 80, and the median score of the domain "normalcy of diet" in the PSS-HN was 91. CONCLUSION: The oncologic outcomes are comparable to the results of open surgery for early and advanced supraglottic carcinomas. Functional swallowing outcome is superior to open surgery and to concomitant chemoradiation. Patients treated with TLM perceive low levels of voice- and swallowing-related quality of life impairment.

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.

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.

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.

Influence of HPV-status on survival of patients with tonsillar carcinomas (TSCC) treated by CO2-laser surgery plus risk adapted therapy - A 10 year retrospective single centre study.

The positive prognostic value of HPV-infections in oropharyngeal squamous cell cancer (OSCC) patients has led to the initiation of prospective clinical trials testing the value of treatment de-escalation. It is unclear how to define patients potentially benefiting from de-escalated treatment, whether a positive smoking history impacts survival data and what kind of de-escalation might be best. Here, we investigate the effect of HPV-status, smoking habit and treatment design on overall survival (OS) and progression free survival (PFS) of 126 patients with tonsillar SCC (TSCC) who underwent CO2-laser-surgery and risk adapted adjuvant treatment. HPV-DNA-, HPV-mRNA-, and p16INK4A-expression were analysed and results were correlated to OS and PFS. Factors tested for prognostic value included HPV-status, p16INK4A-protein expression, therapy and smoking habit. Log rank test and p-values ≤0.05 defined significant differences between groups. The highest accuracy of data with highest significance in this study is given when the HPV-RNA-status is considered. Using p16INK4A-expression alone or in combination with HPV-DNA-status, would have misclassified 23 and 7 patients, respectively. Smoking fully abrogates the positive impact of HPV-infection in TSCC on survival. Non-smoking HPV-positive TSCC patients show 10-year OS of 100% and 90.9% PFS when treated with adjuvant RCT. The presented data show that high-precision HPV-detection methods are needed, specifically when treatment decisions are based on the results. Furthermore, smoking habit should be included in all studies and clinical trials testing HPV-associated survival. Adjuvant RCT especially for HPV-positive non-smokers may help to avoid distant failure.

miRNA-expression in tonsillar squamous cell carcinomas in relation to HPV infection and expression of the antileukoproteinase SLPI.

The aim of this study was to determine if micro-(mi-)RNAs are involved in the previously reported inverse correlation between the antileukoproteinase SLPI, HPV, and smoking habit of head and neck squamous cells carcinoma (HNSCC) patients. HPV-status and SLPI-protein expression were determined in tonsillar SCC (TSCC; n=126). Differentially expressed miRNAs dependent on HPV-status and SLPI-expression were detected by microarray; possible binding-sites in SLPI- and HPVE6-mRNAs were determined in silico. Survival rates were estimated testing prognostic values of HPV-status, SLPI- and miRNA-expression. miRNA-array identified 24 up-regulated and 10 down-regulated miRNAs in HPV-positive versus HPV-negative TSCC (p<0.01; HPV-positivity: 42.1%). HPV-positivity resulted in two up-regulated miRNAs in SLPI-positive TSCC. Of 16 further miRNAs, eight miRNAs were up- and eight were down-regulated in SLPI-negative TSCC. RT-q-PCR-validation of the four most differentially expressed miRNAs showed that miR-363 is expressed strongest in SLPI-negative/HPV-positive TSSC. In silico-analysis of all differentially expressed miRNAs identified miR-363, miR-210, miR-130a, and miR-181a with possible binding sites in the HPV16-E6-mRNA, but none were predicted in the SLPI-mRNA. HPV-positivity, low SLPI-levels and high miR-363-levels are significantly associated with better survival rates. The data presented here show that miR-363 is associated with HPV-positive/SPLI-negative TSCC. The prognostic value of miR-363 suggests a role in the assumed inverse correlation of smoking and SPLI-expression in the mode of HPV-infections in tonsillar but possibly also other HNSCC.

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.

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.

Self-perception versus professional assessment of functional outcome after ablative surgery in patients with oral cancer.

PURPOSE: The extent of functional impairment after ablative surgery in the orofacial region may be directly reflected in a reduction in Quality of Life. This study intended to compare the patients' perception with an objective functional evaluation of the orofacial system in order to bilaterally distinguish direct influence factors. METHODS: A total of 45 patients were included in this study and were asked to complete the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-30) and the Head and Neck 35 Module (H&N 35). Afterward one independent speech therapist evaluated the patients applying the Frenchay Dysarthria Assessment regarding four main categories: mouth opening, tongue motility, swallowing and intelligibility. Comparisons between groups were performed using Whitney-Mann U-Wilcoxon test and calculating Spearman's rho. RESULTS: Overall the professional assessments by the speech therapists revealed significantly higher scores regarding intelligibility, swallowing and mouth opening when compared to the patients' self-perception. Smaller tumor sizes, no bone resection and local reconstruction techniques led to significantly better functional outcomes, when assessed by speech therapists. Swallowing was perceived significantly better by patients in cases of local reconstruction. CONCLUSIONS: From the professionals' point of view differences were perceived in more items compared to the patients' self-assessments, who widely experienced a more severe functional impairment. Physicians should take this into account when discussing adverse therapy effects with the patients.

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.

Prevention of surgical site sternal infections in cardiac surgery: a two-centre prospective randomized controlled study.

OBJECTIVES: Surgical site infection (SSI) of the sternum is a devastating complication in cardiac surgery. The aim of this prospective randomized controlled two-centre clinical study was to compare the use of a gentamicin-collagen sponge (Genta-Coll® resorb) and of a cyanoacrylate-based microbial skin sealant (InteguSeal®) on the SSI rate of the sternum. METHODS: We analysed data from 996 consecutive patients following isolated coronary artery bypass grafting between 2012 and 2014. The patients were randomized into three groups: standard group (S-group), Genta-Coll group (G-group) and InteguSeal group (I-group). The primary study end-point was to analyse the incidence of superficial and deep sternal SSI. The secondary study end-point was to determine independent risk factors for an increased SSI rate. RESULTS: Of the 996 patients investigated, 332 patients were in S-group, 336 patients in G-group and 328 patients in I-group. The mean age was 67.7 ± 9.4 years, 18.6% were women and the overall SSI rate was 6.2% with 2.2% deep sternal wound infections. SSI rates were 8.3% (S-group), 5.4% (G-group) and 4.9% (I-group) (P 0.16). Multiple regression analysis demonstrated a preoperative body mass index (BMI) of >30 kg/m2 (P 0.047), re-thoracotomy for postoperative bleeding (P < 0.001) and sternum instability (P < 0.001) as independent predictors for an increased SSI rate. CONCLUSIONS: The application of InteguSeal® or Genta-Coll® resorb had no significant influence on the incidence of the sternal SSI rate in 996 consecutive cardiac surgery patients but demonstrated a trend towards a benefit from using these prophylactic approaches. Multiple regression analysis demonstrated a preoperative BMI of >30 kg/m2, re-thoracotomy for bleeding and sternum instability as independent predictors for an increased sternal SSI rate.