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Background To assess the hysterectomy probability by calendar period and age, the overall and the age-specific prevalence of hysterectomy in women aged 30–65 years. Methods Baseline data (2005–2007) from the population-based MARZY study conducted in Mainz and Mainz-Bingen, Germany, were analysed. 6429 women aged 30–65 years were asked whether they had undergone a hysterectomy and the date and indication of the procedure. We calculated the 5-year age-specific prevalence of hysterectomy and estimated the probability of undergoing a hysterectomy combining two approaches: 1) Kaplan–Meier and 2) Inverse probability weighting (IPW). We assessed potential changes over calendar periods by simulating survival curves, having hysterectomy as the event, employing a Cox proportional hazard model. Results Data on hysterectomy were available for 4719 women. Of these, 961 (20.4%) had undergone a hysterectomy between 1960 and 2006. The hysterectomy prevalence was highest among the 60–64 year-olds (40.7%). The IPW-corrected probability of having a hysterectomy up to the age of 65 years was 36.4%. The age-specific probability of hysterectomy increased from 0.1% (20–24 years), peaking at 45–49 years (7.8%) and declining thereafter to less than 5% among women aged 50 and older. Over time, women were hysterectomised at an increasingly older age. Most hysterectomies (86.7%) were done due to benign disease. Conclusions A shift to older age at hysterectomy with an advancing calendar period likely reflects changes in clinical practice in Germany. Trial registration Landesärztekammer Rheinland-Pfalz: 837.438.03 (4100).

Background: Diagnosis of allergic rhinitis is achieved by a combination of patient history and different screening tools, followed by specific provocation testing. Screening tools usually involve a skin prick test (SPT), specific serum IgE or a combination of both. Objective: The purpose of this study was to evaluate the correlation of SPT, intradermal testing and specific serum IgE testing in certain allergens and to evaluate sensitization rates, symptom patterns and time of symptoms in a cohort of patients with suspected allergic rhinitis. Methods: Data on 4653 patients with suspected allergic rhinitis were included and divided into five groups: spring bloomers (birch, hazel, etc.), summer bloomers (grasses and rye), autumn bloomers (ribwort and mugwort), mites and mold. Correlation of SPT, intradermal testing and specific IgE test results using Cohen’s kappa and logistic regression were carried out to evaluate the probability of symptoms. Results: Comparison of SPT and specific serum IgE led to kappa coefficients between 0.33 and 0.47, corresponding to a minor to moderate concordance. Comparing the symptoms reported by patients with sensitization diagnosed by SPT, a correlation was only found for spring and summer bloomers with an odds ratio of 1.5 and 2.1, respectively. The most prevalent symptom in the study cohort was rhinitis, followed by others such as asthma, sense of smell and atopic dermatitis. Conclusions: SPT seems to be more sensitive than specific IgE for detection of sensitization. Patients’ symptoms as well as the timing of symptoms, especially for perennial allergies, are not always very pronounced.

Abstract. This study develops a screening method for older patients based on nursing procedure to predict complications associated with cognitive impairment during a hospital stay. This multicenter diagnostic cohort study among older hospitalized patients was carried out in eight primary-care hospitals. Following admission of the patients, trained nurses conducted a structured interview and the Mini-Cog as gold standard for cognitive status; complications during the hospital stay were also monitored. In a second step, the structured interview combined with the Mini-Cog revealed whether there was any abnormality in the interview, making it possible to validly and reliably as well as sensitively and specifically identify patients with a pronounced cognitive impairment who may likely suffer from complications during a hospital stay.

Background Genital involvement in patients with chronic inflammatory skin diseases is frequent, yet insufficiently acknowledged. Objective To evaluate the prevalence of genital symptoms in psoriasis and chronic urticaria patients, effects on quality of life, physician-patient relations and disease management. Patients and methods 100 patients with psoriasis and 100 with chronic urticaria from our outpatient clinic, as well as 50 healthy controls were included. Data was collected using questionnaires developed by dermatological experts. Results Out of 250 subjects, 74 % had already experienced genital symptoms - 70 % of psoriasis patients and 58 % of urticaria patients. Seven out of ten even complained about recurrent genital involvement. 50 % of psoriasis and 41 % of urticaria patients reported an impact on quality of life. 41 % identified genital pruritus as the main symptom, with one out of three expecting a better management for this specific problem. Furthermore, 74 % complained about a lack of awareness among physicians: 79 % of urticaria patients and 58 % of psoriasis patients reported never having been questioned about genital symptoms by their physicians. Conclusions The majority of patients with psoriasis and chronic urticaria suffer from genital involvement and an impaired quality of life. Patient and physician reported outcomes should include genital symptoms as an influencing factor for quality of life.

OBJECTIVES To determine whether the Mini-Cog can be applied by nursing staff to hospitalized elderly patients for cognitive impairment associated risk stratification. METHODS This explorative prospective multicenter cohort study was carried out among 2522 patients aged 70 and older, hospitalized due to physical illness in eight hospitals in Rhineland-Palatinate, Germany. All patients were asked to conduct the Mini-Cog at the day of admission and were clustered into low-performance, intermediate-performance, and good-performance categories by trained nursing staff and two experienced geronto-psychiatrists as gold standard. Complications in the course of the treatment were monitored. RESULTS The Mini-Cog was conducted in 1398 (54%) out of 2522 eligible patients. Mini-Cog scores assessed by nursing staff differed from the gold standard in 327 cases (23.9%). According to the area under the curve (AUC), nursing staff identified cognitively low-performing patients almost as well as the geronto-psychiatrists (AUC = 0.862; 95% CI, 0.83-0.89; P

PURPOSE The positron emission tomography ligand [18 F]MK-9470 is an inverse agonist that binds reversibly and with high affinity to the cannabinoid type 1 receptor. Due to its slow brain kinetics, care is required in the definition of its dissociation rates from the receptor. The goal of this study was to investigate pharmacokinetic analysis methods using an arterial input function. METHODS Five Sprague-Dawley rats received injections of 13 to 25 MBq of [18 F]MK-9470 and were scanned over a period of 90 min. Arterial blood samples were collected throughout the scan. Data were analyzed using four different compartmental models: a reversible one-tissue model, reversible two tissue models with and without parameter constraints and an irreversible two-tissue model. The outcome values were goodness of fit measures (Akaike information criterion; standard error), pharmacokinetic modeling parameters (volume of distribution; irreversible uptake constant) and intersubject variability. RESULTS Goodness of fit measures indicated that the experimental data are more adequately described by a two-tissue model than a one-tissue model. Differences in mean Akaike information criterion values between all two-tissue models were < 5%. Mean standard errors of model parameters were lowest for the irreversible model (range: 1% to 6%). The irreversible model delivered plausible results for all animals that were less variable compared to results of the other two-tissue models. CONCLUSIONS A reversible two-tissue model may not deliver stable results for all animals and regions within a 90-min microPET study protocol. Stable parameters for all animals and regions are obtained when an irreversible model is used. If the acquisition time of the experiment is limited, an irreversible model provides a consistent distribution of composite outcome parameters, suggesting its suitability for use in future studies.

Background The influence of surgery on olfaction in patients who suffer from chronic rhinosinusitis (CRS) is still not fully understood. Most particularly, the time course of the recovery is poorly studied. Methods The prospective study describes the results of the Sniffin' Sticks identification test in 41 subjects before (V1), 2 weeks after (V2), and 6 months after (V3) endonasal sinus surgery (ESS). Influencing factors (gender, revision surgery, nasal polyposis, and initial olfactory score) on the changes of the smell testing were evaluated. Results The whole cohort showed a significant improvement in Identification scores, from 8.63 to 10.24 after 2 weeks and to 10.68 after 6 months. Patients with nasal polyps revealed a similar increase in the identification test at V3 (+2.17 compared to +1.89 in those without polyps) but not at V2 (+1.30 compared to 2.00). The initial classification of olfaction was the only significant influencing factor. Patients who showed initially anosmic results improved (+4.87 at V2 and +4.73 at V3), as did patients in the hyposmic group (+0.58 resp. +1.42). Forty-four percent of the patients reached an improvement with regard to their diagnostic group. Conclusions This study of the evaluation of the sense of smell after ESS exhibits an improvement of olfaction already 2 weeks after surgery, which is stable for 6 months. CRSwNP and CRSsNP patients showed similar improvements of olfaction, although the recovery was slower in CRSwNP patients. Level of Evidence 2b

The endocannabinoid system participates in many processes in the body, including memory, reward, pain, motor activity, food intake, energy metabolism, and gastrointestinal functions. [18F]MK-9470 is a positron emission tomography (PET) ligand that binds with high affinity and selectivity to the cannabinoid type 1 receptor. In order to fully characterize ligand behavior, tracer uptake measured using in vivo microPET was compared with results from ex vivo tissue dissection. Twelve male Sprague-Dawley rats were divided into three subgroups and scanned over time periods of 10min, 30min and 90min using PET. Afterwards, a number of the animals' organs were dissected. Uptake of radioactivity was expressed in terms of %ID/ml and %ID/(g tissue). For comparison of in vivo and ex vivo methods, Bland-Altman plots were computed. The highest uptake of [18F]MK-9470 was found in the liver and small intestine; the brain showed less uptake, while low and unspecific binding was observed in tissue of the heart, lung, kidney and bone. In the brain, normalized uptake of [18F]MK-9470 was on average 0.25%ID/ml (range: 0.16 to 0.28%ID/ml). Bland-Altman plots revealed the best agreement between methods for the 90min acquisition protocols. High hepatic accumulation and metabolism of [18F]MK-9470 occur with mainly enteral excretion, which may vary considerably over time - a finding which may be of relevance in metabolite determination in quantitative brain studies. Comparisons between in vivo and ex vivo methods showed that whole-body distribution of [18F]MK-9470 using positron emission tomography is a preferable alternative to ex vivo biodistribution, and requires a significantly smaller number of animals.

Δ9-Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [18F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies.

Background Autoimmune thrombotic thrombocytopenic purpura (iTTP) is caused by autoantibody-mediated severe a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13) deficiency leading to micro-angiopathic haemolytic anaemia (MAHA) and thrombocytopenia with organ damage. Patients survive with plasma exchange (PEX), fresh frozen plasma replacement and corticosteroid treatment. Anti-CD20 monoclonal antibody rituximab is increasingly used in patients resistant to conventional PEX or relapsing after an acute bout. Objective This retrospective observational study focused on the relapse rate and possible influencing factors including treatment with rituximab first introduced in 2003. Patients and Methods Seventy patients treated between January 2003 and November 2014 were evaluated. Number, duration, clinical manifestations, laboratory data and treatment of acute episodes were documented. Diagnostic criteria of acute iTTP were thrombocytopenia, MAHA, increased lactate dehydrogenase and severe ADAMTS13 deficiency. Results Fifty-four female and 16 male patients had a total of 224 acute episodes over a median observation period of 8.3 years. The relapse rate was 2.6% per month, for women 2.4% and for men 3.5% per month. Since 2003, 17 patients with a first iTTP episode were treated with rituximab, whereas 28 were not. There was a trend towards lower relapse rates after rituximab treatment over the ensuing years. However, this was statistically not significant. Conclusion This analysis does not show a significant reduction of acute iTTP relapses by rituximab given during an acute bout. Initial episodes are characterized by more severe clinical signs compared with the less severe relapses. Furthermore, men suffer significantly more frequent and considerably more serious acute relapses.

Background: Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays an important role as a mediator of cell migration, invasion, proliferation and survival. Conflicting results for the prognostic role of FAK in breast cancer (BC) prompted us to determine its impact. Methods: Patients with node-negative BC entered this retrospective study. FAK expression was determined by immunohistochemistry (n = 335). The prognostic impact of FAK was examined with Cox regression analyses and Kaplan-Meier estimation in the whole cohort as well as in different molecular subtypes. Results: 151 (45.1%) had a FAK-positive BC. In univariate analyses, FAK expression showed a significant impact for shorter disease-free survival (DFS) (hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.04-2.28, p = 0.030) but not for metastasis-free survival and overall survival. Significant prognostic relevance for DFS (HR 1.76, 95% CI 1.05-2.97, p = 0.033) was observed in particular in estrogen receptor-positive HER2-negative BC patients, most notably in luminal B-like tumors (HR 2.32, CI 1.20-4.48, p = 0.012). However, FAK lost its prognostic impact in multivariate Cox regression analysis. Conclusion: FAK was associated with impaired DFS in univariate analysis. Prognostic relevance for DFS was most pronounced in luminal B-like BC. However, FAK expression was not associated with an independent impact on survival for BC in multivariate analysis.

Background The clinical importance of tumor-infiltrating cluster of differentiation 4 (CD4) T cells is incompletely understood in early breast cancer. We investigated the clinical significance of CD4, forkhead box P3 (FOXP3), and B cell attracting chemokine leukocyte chemoattractant-ligand (C-X-C motif) 13 (CXCL13) in early breast cancer. Methods The study is based on the patient population of the randomized FinHer trial, where 1010 patients with early breast cancer were randomly allocated to adjuvant chemotherapy containing either docetaxel or vinorelbine, and human epidermal growth factor receptor 2 (HER2)-positive patients were also allocated to trastuzumab or no trastuzumab. Breast cancer CD4, FOXP3, and CXCL13 contents were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), and their influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates in the entire cohort and in selected molecular subgroups. Interactions between variables were analyzed using Cox regression. The triple-negative breast cancer (TNBC) subset of the HE10/97 randomized trial was used for confirmation. Results High CXCL13 was associated with favorable DDFS in univariable analysis, and independently in multivariable analysis (HR 0.44, 95% CI 0.29–0.67, P ≤ 0.001), most strongly in TNBC (HR 0.39, 95% CI 0.19–0.79, P = 0.009). No significant interaction with chemotherapy or trastuzumab administration was detected. Neither tumor CD4 content nor FOXP3 content was associated with DDFS. The favorable prognostic influence of CXCL13 was confirmed in the HE10/97 trial patient population with TNBC (HR 0.30, 95% CI 0.09–0.93; P = 0.038). Conclusions The results provide a high level of evidence that humoral immunity influences the survival outcomes of patients with early breast cancer, in particular of those with TNBC. Trial registration The study reports retrospective biomarker analyses in the prospective FinHer trial and the prospective HE10/97 trial. ISRCTN76560285. Registered on 18 March 2005. ACTRN12611000506998. Registered on 16 May 2011. Electronic supplementary material The online version of this article (10.1186/s13058-018-0942-x) contains supplementary material, which is available to authorized users.

Objectives Sleep problems are often assessed using questionnaires, but it is unclear whether the responses given are influenced by age and gender. We addressed this question in several widely used pediatric sleep questionnaires and provide age-dependent percentile curves. Methods Data of a community-based study in schoolchildren were reanalyzed (N = 163, 50% males, age 6–17 years). Children and their parents completed the Sleep-Related Breathing Disorder Scale (SRBDS) of the Pediatric Sleep Questionnaire, the Sleep Disturbance Scale for Children (SDSC), the Sleep Self Report (SSR) of the Children's Sleep Habits Questionnaire in a long and short version, the Epworth Sleepiness Scale in a parent- (ESSp) and self-report version for children (ESSc), and the Pediatric Daytime Sleepiness Scale (PDSS). Linear and quantile regression analysis was used to i) assess the influence of age and gender on scores of questionnaire scales/subscales, ii) to calculate age- and gender-appropriate reference values and iii) to provide age-depending percentile curves. Results Only the PDSS showed relevant gender differences (β [95th confidence interval] = 0.155 [0.000; 0.270], p-value = 0.04, reference category: male), while the following subscales were all age dependent: SRBDS-somnolence and behavioral subscales, SDSC-somnolence subscale, SSR-long and short version; ESSp and ESSc, as well as the PDSS. Conclusions Age and gender should be taken into account for research purposes and individual patient assessments regarding sleep problems. Preliminary age- and gender-appropriate reference values and percentile curves are now available and may be used by researchers and clinicians.

The positron emission tomography ligand [Five Sprague-Dawley rats received injections of 13 to 25 MBq of [Goodness of fit measures indicated that the experimental data are more adequately described by a two-tissue model than a one-tissue model. Differences in mean Akaike information criterion values between all two-tissue models were5%. Mean standard errors of model parameters were lowest for the irreversible model (range: 1% to 6%). The irreversible model delivered plausible results for all animals that were less variable compared to results of the other two-tissue models.A reversible two-tissue model may not deliver stable results for all animals and regions within a 90-min microPET study protocol. Stable parameters for all animals and regions are obtained when an irreversible model is used. If the acquisition time of the experiment is limited, an irreversible model provides a consistent distribution of composite outcome parameters, suggesting its suitability for use in future studies.

Purpose The major goal of this study was to test the hypothesis that in patients with peripheral hypertrophic subepithelial corneal opacification (PHSCO), visualization of corneal vessels is better with optical coherence tomography angiography (OCTA) than with conventional slit lamp microphotography. Methods Patients with PHSCO were included in this prospective study. The corneal findings were photographed using a slit lamp camera (Haag Streit BM 900® ) and visualized with anterior-segment OCT (Optovue XR Avanti, Fremont, California, USA). Additionally, OCTA with the Angiovue Imaging™ System was performed in the area of PHSCO. Results Thirty-four eyes of 19 patients (26% male and 74% female) with PHSCO were included in this study. In 21 eyes, vascularization in the area of PHSCO was visualized with the Angiovue-OCT, whereas only 10 eyes presented vessels in slit lamp photographs. Conclusion Optical coherence tomography angiography allows better visualization of corneal neovascularization than slit lamp photography in patients with PHSCO. Corneal opacifications were found predominantly nasally, which was reflected by a local enlargement of corneal thickness.

Background The influence of surgery on olfaction in patients who suffer from chronic rhinosinusitis (CRS) is still not fully understood. Most particularly, the time course of the recovery is poorly studied. Methods The prospective study describes the results of the Sniffin' Sticks identification test in 41 subjects before (V1), 2 weeks after (V2), and 6 months after (V3) endonasal sinus surgery (ESS). Influencing factors (gender, revision surgery, nasal polyposis, and initial olfactory score) on the changes of the smell testing were evaluated. Results The whole cohort showed a significant improvement in Identification scores, from 8.63 to 10.24 after 2 weeks and to 10.68 after 6 months. Patients with nasal polyps revealed a similar increase in the identification test at V3 (+2.17 compared to +1.89 in those without polyps) but not at V2 (+1.30 compared to 2.00). The initial classification of olfaction was the only significant influencing factor. Patients who showed initially anosmic results improved (+4.87 at V2 and +4.73 at V3), as did patients in the hyposmic group (+0.58 resp. +1.42). Forty‐four percent of the patients reached an improvement with regard to their diagnostic group. Conclusions This study of the evaluation of the sense of smell after ESS exhibits an improvement of olfaction already 2 weeks after surgery, which is stable for 6 months. CRSwNP and CRSsNP patients showed similar improvements of olfaction, although the recovery was slower in CRSwNP patients. Level of Evidence 2b.

Purpose Intraocular pressure (IOP) fluctuation is considered as a risk factor for glaucoma progression. We investigated IOP values and IOP fluctuation before and after trabeculectomy (TE) with mitomycin C (MMC) measured by 48-hour diurnal-nocturnal-IOP-profiles (DNP). Methods Pre- and postoperative DNPs of 92 eyes undergoing primary TE with MMC were analysed. Each 48-hour IOP-profile involved 10 IOP measurements (8:00 a.m., 2:00 p.m., 6:00 p.m., and 9:00 p.m. in sitting and at 00:00 in supine position). The “preoperative DNP” was performed a few weeks before TE. The “postoperative DNP” was performed at least six months (range: 6 months—2 years) after TE. Mean IOP values and IOP fluctuations were calculated. Results After TE with MMC mean IOP was reduced from 16.94±3.83 to 11.26±3.77 mmHg at daytime and from 18.17±4.26 to 11.76±3.90 mmHg at night. At daytime mean IOP-fluctuation decreased from 8.61±4.19 to 4.92±2.52 mmHg, at night from 3.15±2.95 to 1.99±1.82 mmHg. Mean IOP was lower on the second day of the preoperative DNP. This effect was not present in the postoperative DNP. Preoperatively, IOP was controlled in all eyes with a mean of 3.22±0.94 antiglaucomatous agents. Postoperatively, IOP≤15 mmHg was achieved in 71.7%, IOP≤18 mmHg in 77.1% and a decrease in IOP of >30% in 47.8% without antiglaucomatous therapy. Postoperatively, pseudophakia was associated by a higher mean IOP-fluctuation compared to the phakic eyes. Conclusions TE with MMC significantly reduces both mean IOP-values and IOP- fluctuations at day and night at least 6 months postoperatively. The effect of TE on the IOP fluctuation was less pronounced in pseudophakic eyes.

The precise determination of energy metabolites is challenged by the heterogeneity of their distribution, their rapid changes after surgical resection and the architectural complexity of malignancies. Induced metabolic bioluminescence imaging (imBI) allows to determine energy metabolites in tissue sections and to co-localize these with histological structures based on consecutive sections stained with HE. In this prospective pilot study patients with suspected advanced ovarian cancer (OC) were enrolled to prove the feasibility of imBI. During surgery, suspicious peritoneal metastases were resected and transferred in liquid nitrogen within 30 s. ATP, glucose and lactate concentrations were measured. Furthermore, the expression of monocarboxylate transporters MCT1 and MCT4 was determined by immunofluorescence staining. 16 patients were screened, 12 entered the study. Final histological assessment revealed ten malignant and two benign peritoneal lesions. In all 12 cases high concentrations of ATP suggested that energy metabolism was not altered by the surgical and transport procedures (mean 0.56 μmol/g, range 0.24–1.21 μmol/g). The mean concentration of glucose was 1.95 μmol/g (range 0.58–4.71 μmol/g). The concentration of lactate was drastically higher in the ten OC cases (mean 24.79 μmol/g, range 17.51–37.16 μmol/g) compared to the benign samples (mean 5.98 μmol/g, range 5.43–6.54 μmol/g). Lactate concentrations seem to correlate with MCT1 (spearman rank correlation ρ = 0.624, 0.05 > p > 0.025), but not with MCT4 (spearman rank correlation ρ = 0.018, p > 0.1). ImBI is feasible in peritoneal metastases of OC and encourages further effort to elucidate the role of glucose, lactate, MCT1 and MCT4 in OC.

e17093Background: The precise determination of energy metabolites is challenged by the heterogeneity of their distribution, their rapid changes after surgical resection and the architectural comple...