[Midwives as influencers in skin care for newborns at risk of atopic diseases : Survey of midwives' current recommendations]. / Hebammen als Influencer bei der Hautpflege atopisch prädisponierter Neugeborener : Eine Umfrage zu den aktuellen Empfehlungen von Hebammen.

INTRODUCTION: The prevalence of atopic diseases remains high. Initial studies suggest that primary prevention with regular basic care may influence the incidence of atopic dermatitis in infants; however, data are unclear. Midwives play an important role in the care of women in the peripartum period and therefore also in providing advice on topics such as skin care, breastfeeding and nutrition of the newborn and young infant. The aim of this study was to determine the care recommendations for newborns by midwives. METHODS: We conducted a cross-sectional survey among German midwives using questionnaires on the topic of newborn skin care. RESULTS: A total of 128 questionnaires were analyzed. The most common recommendations were oil-based herbal topicals (34.9%) and plain water (34.0%). Approximately 70% of midwives reported recommending various options when there was a known family history of atopic diathesis. It was remarkable that most of the midwives' recommendations were identical regardless of the presence of an atopic diathesis. Essential care products are only used "when necessary". CONCLUSION: Training programs for midwives on the topic of "care and strengthening of the skin barrier", taking into account the current guidelines for allergy prevention, should be implemented.

Breast cancer screening with digital breast tomosynthesis: Is independent double reading still required? / Brustkrebs-Screening mit digitaler Brust-Tomosynthese: Ist weiterhin eine unabhängige Doppelbefundung erforderlich?

PURPOSE: The European guidelines recommend independent double reading in mammography screening programs. The prospective randomized controlled trial TOSYMA tested the superiority of digital breast tomosynthesis and synthetic mammography (DBT+SM) over digital mammography (DM) for invasive breast cancer detection. This sub-analysis compares the true-positive readings of screening-detected breast cancers resulting from independent double readings in the two trial arms. MATERIALS AND METHODS: The 1:1 randomized TOSYMA trial was executed in 17 screening units between 07/2018 and 12/2020. This sub-analysis included 49,762 women in the test arm (DBT+SM) and 49,796 women in the control arm (DM). The true-positive reading results (invasive breast cancers and ductal carcinoma in situ) from 83 readers were determined and merged in a double reading result. RESULTS: DBT+SM screening detected 416 women with breast cancer and DM screening detected 306. Double readings of DBT+SM examinations led to a single true-positive together with a single false-negative result in 26.9 % of cancer cases (112/416), and in 22.2 % of cases (68/306) in the DM examinations. The cancer detection rate with discordant reading results was 2.3 per 1,000 women screened with DBT+SM and 1.4 per 1,000 with DM. Discordant reading results occurred most often for invasive breast cancers [DBT+SM 75.9 % (85/112), DM 67.6 % (46/68)], category T1 [DBT+SM 67.9 % (76/112), DM 55.9 % (38/68)], and category 4a [DBT+SM: 67.6 % (73/112); DM: 84.6 % (55/68)]. CONCLUSION: The higher breast cancer detection rate with DBT screening includes a relevant percentage of breast cancers that were only detected by one reader in an independent double reading. As in digital mammography, independent double reading continues to be justified in screening with digital breast tomosynthesis. KEY POINTS: · The percentages of discordant cancer reading results were 26.9 % and 22.2 % for DBT+SM and DM, respectively.. · The single true-positive detection rate was 2.3 ‰ for DBT+ SM and 1.4 ‰ for DM.. · A relevant proportion of screening-detected cancers resulted from a single true-positive reading.. CITATION FORMAT: · Weigel S, Hense HW, Weyer-Elberich V et al. Breast cancer screening with digital breast tomosynthesis: Is independent double reading still required?. Fortschr Röntgenstr 2024; DOI: 10.1055/a-2216-1109.

Digital Breast Tomosynthesis versus Digital Mammography for Detection of Early-Stage Cancers Stratified by Grade: A TOSYMA Subanalysis.

Background Breast cancer screening with digital breast tomosynthesis (DBT) plus synthesized mammography (SM) increases invasive tumor detection compared with digital mammography (DM). However, it is not known how the prognostic characteristics of the cancers detected with the two screening approaches differ. Purpose To compare invasive breast cancers detected with DBT plus SM (test arm) versus DM (control arm) screening with regard to tumor stage, histologic grade, patient age, and breast density. Materials and Methods This exploratory subanalysis of the Tomosynthesis plus Synthesized Mammography (TOSYMA) study, which is a multicenter randomized controlled trial embedded in the German mammography screening program, recruited women aged 50-70 years from July 2018 to December 2020. It compared invasive cancer detection rates (iCDRs), rate differences, and odds ratios (ORs) between the arms stratified by Union for International Cancer Control (UICC) stage (I vs II-IV), histologic grade (1 vs 2 or 3), age group (50-59 vs 60-70 years), and Breast Imaging Reporting and Data System categories of breast density (A or B vs C or D). Results In total, 49 462 (median age, 57 years [IQR, 53-62 years]) and 49 669 (median age, 57 years [IQR, 53-62 years]) participants were allocated to DBT plus SM and DM screening, respectively. The iCDR of stage I tumors with DBT plus SM was 51.6 per 10 000 women (255 of 49 462) and with DM it was 30.0 per 10 000 women (149 of 49 669). DBT plus SM depicted more stage I tumors with grade 2 or 3 (166 of 49 462, 33.7 per 10 000 women) than DM (106 of 49 669, 21.3 per 10 000 women; rate difference, +12.3 per 10 000 women [95% CI: 0.3, 24.9]; OR, 1.6 [95% CI: 0.9, 2.7]). DBT plus SM achieved the highest iCDR of stage I tumors with grade 2 or 3 among women aged 60-70 years with dense breasts (41 of 7364, 55.4 per 10 000 women; rate difference, +21.6 per 10 000 women [95% CI: -21.1, 64.3]; OR, 1.6 [95% CI: 0.6, 4.5]). Conclusion DBT plus SM screening appears to lead to higher detection of early-stage invasive breast cancers of grade 2 or 3 than DM screening, with the highest rate among women aged 60-70 years with dense breasts. Clinical trial registration no. NCT03377036 © RSNA, 2023 See also the editorial by Ha and Chang in this issue.

Morphology of the knee after guided growth using tension-band devices: a retrospective multicenter study of 222 limbs and 285 implants.

BACKGROUND AND PURPOSE: Temporary hemiepiphysiodesis by tension-band devices is commonly applied to correct angular limb deformities in children. We aimed to evaluate knee joint morphology after guided growth using these devices. PATIENTS AND METHODS: In a retrospective multicenter study we analyzed standardized anteroposterior long-leg radiographs of 222 limbs (285 implants) of patients treated by temporary hemiepiphysiodesis with either eight-Plates or FlexTacks for coronal angular deformities of the knee joint between 2013 and 2019. Femoral floor angle (FFA), femoral notch-intercondylar distance (FNID), and tibial roof angle (TRA) were measured pre- and postoperatively to assess the central knee joint morphology. Statistical exploratory analyses were performed using linear mixed models, t-tests, Wilcoxon signed-rank test, and Mann-Whitney U test. RESULTS: 217 FlexTacks (femur 106, tibia 111) in 104 children and 68 eight-Plates (femur 61, tibia 7) in 35 children were identified. Median time period under growth guidance was 11 months (range 4-42). No statistically significant change in the FFA was detected (eight-Plate: P = 0.2; FlexTack: P = 0.3). A statistically significant difference of the FNID was found in the eight-Plate group (P = 0.02), but not in the FlexTack group (P = 0.3). While TRA increased in both groups, a statistical significance was observed only in the FlexTack group (P < 0.01). CONCLUSION: We found minor but clinically irrelevant changes in knee morphology after the treatment.

Radiographic reference values of the central knee anatomy in 8-16-year-old children.

BACKGROUND AND PURPOSE: For correction of leg-length discrepancy or angular deformity of the lower limb in skeletally immature patients temporary or permanent (hemi-)epiphysiodesis can be employed. These are reliable treatments with few complications. Recently, radiographic analysis of treatment-related alterations of the central knee anatomy gained interest among pediatric orthopedic surgeons. To date the comparison and adequate interpretation of potential changes of the central knee anatomy is limited due to the lack of defined standardized radiographic references. We aimed to establish new reference values of the central knee anatomy. PATIENTS AND METHODS: A retrospective analysis of calibrated longstanding anteroposterior radiographs of 254 skeletally immature patients with a chronological age ranging from 8 to 16 years was conducted. The following radiographic parameters were assessed: (1) femoral floor angle, (2) tibial roof angle, (3) width at femoral physis, and (4) femoral notch-intercondylar distance. RESULTS: All observed radiographic parameters were normally distributed with a mean age of 12.4 years (standard deviation [SD] 2, 95% confidence interval [CI] 12.2-12.6). Mean femoral floor angle was 142° (SD 6, CI 141.8-142.9), mean tibial roof angle was 144° (SD 5, CI 143.7-144.1), mean width at femoral physis was 73 mm (SD 6, CI 72.8-73.9), and mean femoral notch-intercondylar distance was 8 mm (SD 1, CI 7.5-7.7). The estimated intraclass correlation coefficient values were excellent for all measurements. CONCLUSION: This study provides new radiographic reference values of the central knee anatomy for children between 8 and 16 years and we suggest considering values within the range of 2 SD as the physiological range.

Changes in the probability of hysterectomy in the city of Mainz and Mainz-Bingen region, Germany.

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).

High prevalence and little awareness in patients with chronic inflammatory skin diseases and genital involvement.

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.

Early deaths from childhood cancer in Germany 1980-2016.

BACKGROUND: Even though the survival of childhood cancer has improved over the last decades, there are still children dying shortly after diagnosis. The aim of the study is to add to understanding of the reasons for deaths shortly after date of diagnosis. METHODS: Using data of the population-based German Childhood Cancer Registry (cancer below 15 years of age diagnosed between 1980 and 2016), we compared characteristics of 671 children with cancer who died within 30 days of diagnosis to 53,649 patients with childhood cancer who survived longer. In addition to a descriptive analysis, we used logistic regression with multivariable fractional polynomials to describe the relationship between early death with age at diagnosis and year of diagnosis. RESULTS: The number of early death cases and the risk of early death have decreased considerably since 1980 (2.6% of study population in 1980-89 to 0.6% in 2010-16). Children under one year of age were at highest early death risk (odds ratio = 4.10, 95% confidence interval: 3.32-5.05 compared to 7-year-old patients). These results are similar to results from other studies. Moreover, children with acute myeloid leukemia and hepatic tumors had a higher early death risk, children with acute lymphoid leukemia a lower risk compared to patients with central nervous system tumors used as a reference group. CONCLUSION: Even though the risk for early death has declined overall with advances in diagnosis and therapy, special attention needs to be paid to infants and children with AML and hepatic tumors, who are especially at risk.

Analysis of the Corneal Anterior and Posterior Surface in Patients With Peripheral Hypertrophic Subepithelial Corneal Opacification.

PURPOSE: To characterize the corneal changes in peripheral hypertrophic subepithelial corneal opacification (PHSCO) considering elevation of the anterior and posterior corneal surface, corneal astigmatism, tear secretion, and endothelial cell density. METHODS: Thirty-eight eyes of 22 patients with PHSCO on at least 1 eye and 38 eyes of 22 age- and sex-matched healthy subjects were included in this retrospective cross-sectional study. Using the Pentacam system (Oculus, Wetzlar, Germany), measurement of the anterior and posterior corneal surface was performed. In addition, the Schirmer test was conducted, and endothelial cells were counted in the central cornea with a specular microscope (SP-3000P; Topcon, Tokyo, Japan). RESULTS: The mean age was 55.2±11.7 years in patients with PHSCO and 54.1±12.4 years in healthy subjects. The corneas of patients with PHSCO showed higher corneal astigmatism of both the corneal anterior and posterior surface (2.9/0.5 vs. 0.8/0.3 D, PHSCO vs. controls, P=<0.001/<0.01). The cornea was thickest in the peripheral 12-o'clock position and the peripheral superior nasal area. Remarkably, central endothelial cell density was markedly reduced in patients with PHSCO (2,372.6 cell/mm±328.1 vs. 2,673 cells/mm±287.6, P<0.01, PHSCO vs. controls). Also, the Schirmer test revealed lower tear secretion in patients with PHSCO (9.8±4.4 mm vs. 14.3±5.7 mm, P<0.001, PHSCO vs. controls). CONCLUSION: The astigmatism of both the anterior and posterior corneal surface is increased in patients with PHSCO. Intriguingly, tear secretion and central endothelial cell density are reduced in patients with PHSCO. These measurements may become useful to assess the impact of morphological changes on vision and to track disease progression in PHSCO.

Ocular ductions after rectus muscle recession and resection in thyroid eye disease.

Background: Recession and resection of rectus muscles for correction of strabismus in Thyroid Eye Disease (TED) is relatively unpopular as it is assumed to enhance the restriction of ocular ductions. Therefore, the purpose of this study was to compare ductions of recession only and recess/resect procedures. Methods: We retrospectively reviewed the charts of 119 patients who underwent strabismus surgery for TED from 1991 to 2015, of which 102 were included in the present study. Forty-six interventions were performed on horizontal, 56 on vertical rectus muscles; comprising 41 recess/resect surgeries for horizontal deviations, and 7 in patients with vertical strabismus. Ocular ductions and alignment were evaluated preoperatively and at 3 and 12 months postoperatively. Results: Both recessions as well as recess/resect procedures resulted in improved abduction and elevation, respectively. At the exam 3 months postoperatively, median abduction for the recession only group and the recess/resect group were 27.5° and 35°, respectively. The similar figures for elevation were 25° and 10°, respectively. Neither were statistically significant. No restricted adduction or depression was seen in the recess/resect surgeries groups with lateral or superior rectus resection. None of the patients showed unusual postoperative inflammation or conjunctival scarring. Conclusion: In this retrospective analysis, we found an equal effect on ocular ductions in patients with TED when comparing recess/resect eye muscle surgery to recess only procedures. In TED patients with large horizontal angle deviations and abduction deficit, medial rectus recession and lateral rectus resection surgery can be considered. Muscle resections in TED do not seem to have a clinically relevant risk to increase the restriction of ocular ductions but rather improve ductions in the restricted directions of gaze.

Feasibility and utility of a cognitive screening for risk stratification in hospitalized older patients.

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 < 0.001, accuracy 89.6%). Overall, 241 (17.6%) patients were classified as low performing. These patients had a significantly higher probability of suffering from at least one complication (odds ratio [OR] = 3.13; 95% CI, 2.09-4.70; calculated by a logistic regression model, adjusted for age), and they had a higher probability to show behavioral symptoms. CONCLUSION: Even under naturalistic conditions, nursing staff detected cognitively low-performing inpatients with the Mini-Cog. Using this short screening instrument should enable to predict complications of hospitalized older patients associated with cognitive impairment, a precondition to implement targeted care for this vulnerable patient group.

Relapse Rate in Survivors of Acute Autoimmune Thrombotic Thrombocytopenic Purpura Treated with or without Rituximab.

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.

Influence of age and gender on reference values for common pediatric sleep questionnaires: Results from a community-based study.

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 (ß [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.

Determinants of illness-specific social support and its relation to distress in long-term melanoma survivors.

BACKGROUND: Social support is considered to be one of the most important resources for coping with cancer. However, social interactions may also be detrimental, e. g. disappointing or discouraging. The present study explored: 1. the extent of illness-specific positive aspects of social support and detrimental interactions in melanoma survivors, 2. their relationships to mental health characteristics (e. g. distress, quality of life, fatigue, coping processes, and dispositional optimism) and 3. Combinations of positive social support and detrimental interactions in relation to depression and anxiety. METHODS: Based on the cancer registry of Rhineland-Palatinate, Germany, melanoma patients diagnosed at least 5 years before the survey were contacted by their physicians. N = 689 melanoma patients filled out the Illness-specific Social Support Scale ISSS (German version) and standardised instruments measuring potential psychosocial determinants of social support. RESULTS: Using principal component analysis, the two factor structure of the ISSS could be reproduced with acceptable reliability; subscales were "Positive Support" (PS) and "Detrimental Interactions" (DI); Cronbach's α = .95/.72. PS was rated higher than DI. Multivariable linear regressions identified different associations with psychosocial determinants. Survivors living in a partnership and those actively seeking out support had a higher probability of receiving PS, but not DI. PS and DI interacted regarding their association with distress: Survivors reporting high DI but low PS were the most depressed and anxious. High DI was partly buffered by PS. When DI was low, high or low PS made no difference regarding distress. CONCLUSION: Psycho-oncologic interventions should take into account both positive and negative aspects of support in order to promote coping with the disease.

Visualization of corneal vascularization in peripheral hypertrophic subepithelial corneal opacification with OCT angiography.

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.

Prognostic impact of CD4-positive T cell subsets in early breast cancer: a study based on the FinHer trial patient population.

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.

Pharmacokinetics of the cannabinoid receptor ligand [18 F]MK-9470 in the rat brain - Evaluation of models using microPET.

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.

Prognostic Significance of Focal Adhesion Kinase in Node-Negative Breast Cancer.

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.

Course of olfaction after sinus surgery for chronic rhinosinusitis.

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.