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Background: Aberrant immune responses play a key role in the pathogenesis of inflammatory bowel disease (IBD). Most studies conducted to delineate the underlying molecular mechanisms focus on adults; an understanding of these mechanisms in children remains to be determined. Here, cytokines and transcription factors produced by immune cells within the intestinal mucosa of pediatric patients stricken with ulcerative colitis (UC) and Crohn's disease (CD) are characterized; potential diagnostic and therapeutic targets are identified., Methods: Fifty-two pediatric IBD and non-IBD patients were enrolled in the study. Specimens were taken during ileocolonoscopy. Expression of 16 genes that encode cytokines or transcription molecules was determined by quantitative polymerase chain reaction. Clinical data were collected via retrospective chart review., Results: Overexpression of interleukin-17A (IL-17A) was evident in children with UC compared to both non-IBD and CD patients. IL-22 was strongly increased in UC patients only. Typical proinflammatory and immunoregulatory cytokines were pronounced in IBD patients, although to a lower extent in the latter case. Clustered gene expression enabled differentiation between UC and non-IBD patients., Conclusion: Our findings highlight the crucial involvement of IL-17A immunity in the early course of IBD, particularly UC, and the potential value of gene panels in diagnosing pediatric IBD.

Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn's disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney U -test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., Eubacterium rectale and Faecalibacterium prausnitzii , were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like Escherichia coli were enriched in UC patients (MWU FDR = 0.084). Moreover, E. coli abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option. NEW & NOTEWORTHY In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD., (Copyright © 2017 the American Physiological Society.)

Hot flushes, night sweats, pain during sexual intercourse, hair loss, forgetfulness, depression and sleeping disturbances are common problems among breast cancer patients undergoing antihormonal treatment. The aim of this study was to investigate whether bee pollen can alleviate menopausal symptoms in patients receiving tamoxifen and aromatase inhibitors/inactivators. We compared a pollen-honey mixture with pure honey (placebo) in a prospective, randomized crossover trial in breast cancer patients receiving antihormonal treatment. The menopausal complaints were assessed using the Menopause Rating Scale (MRS). A total of 46 patients were recruited; 68.3% (28/41) of the patients reported an improvement in their symptoms while taking honey, compared with 70.9% (22/31) who reported an improvement with pollen (the difference was non-significant). The results were confirmed by significant improvements in the postmenopausal complaints in the two groups in a pre-post analysis in the MRS and its 3 subscales. This study provided evidence that honey and bee pollen may improve the menopausal symptoms of breast cancer patients on antihormonal treatment. Of note, honey, which was intended to be used as a placebo, produced similar effects as pollen and they both exceeded the extent of a placebo effect in this setting (~25%).

Background: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses., Patients and Methods: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, β = 0.8) 379 events had to be observed in the bevacizumab arms., Results: With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups., Conclusions: Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients., Clinical Trial Number: NCT 00567554, www.clinicaltrials.gov., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Conflicting evidence has been published concerning survival disadvantages in the outcome of breast cancer patients in relationship to their residency in urban or rural communities., Methods: The primary aim of this study was to evaluate differences in patients and treatment characteristics between an urban and a rural breast cancer unit. Therefore, all early breast cancer patients treated consecutively between 1999 and 2007 in a rural and an urban breast cancer unit were included. Patient and tumor characteristics, treatment strategies, and guideline adherence were included to evaluate the prognoses of both populations., Results: Overall, data from 2,566 patients were included in this analysis. The 610 patients treated in the rural unit showed significantly more negative prognostic criteria than the 1,956 patients treated in the urban center. No differences were observed with respect to surgical and systemic treatment after adjustment for prognostic parameters. Adherence to national guidelines did not differ significantly between both settings and ranged between 78.0 and 95.6%. Furthermore, no differences regarding recurrence-free and overall survival were observed., Conclusions: The stage-adjusted pattern of care was similar in 2 German breast care units in a rural region and an urban area. Nevertheless, an earlier diagnosis of breast cancer should be enforced in rural areas to avoid extended treatment burden., (© 2013 S. Karger GmbH, Freiburg.)

Introduction: At present the topic "feminisation" in medicine, in other words the increasing number of female staff members is under heavy discussion; however, there are only few data upon the basis of which a scientific discussion can be held. The question arises as to the possibility of problems arising therefrom for the specialty gynaecology and obstetrics. Methods: With the help of a questionnaire the directors of departments of gynaecology and obstetrics were questioned about the various aspects of the topic feminisation in gynaecology and obstetrics. Results: Among current applications the proportion of female applicants is estimated to be 84.2 %. Reasons given most frequently for the feminisation in the specialty include low income, loss of face of the medical profession and the poor career chances. Among the spontaneously mentioned reasons were the increasingly female dominated image of gynaecology and the working conditions in hospitals. Whereas the taking on of surgical duties and of directing functions was less markedly desired by women than by men, the questioned directors found that male and female staff members were equally motivated to take on duties outside of their working hours or to engage in research work. Discussion: Feminisation in medicine represents a challenge. It seems to be important to evaluate and investigate the motivation of staff members with regard to their wishes in professional life and thus to be able to offer an appropriate working environment based on the survey results.

Background & Aims: Pegylated interferon (PEG-IFN) alfa-2b plus ribavirin (RBV) is the standard of care for adults with chronic hepatitis C but was not approved for the treatment of children at the time of this study. The aim of this study was to evaluate the efficacy and safety of PEG-IFN alfa-2b plus RBV in children., Methods: Children and adolescents ages 3-17 years were treated with PEG-IFN alfa-2b (60microg/m(2)/week) plus RBV (15mg/kg/day). The duration of therapy was 24 weeks for genotype (G) 2 and G3 patients with low viral load (<600,000IU/ml) and 48 weeks for G1, G4, and G3 with high viral load (>or=600,000IU/ml). The primary end point was sustained virologic response (SVR), defined as undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of therapy., Results: SVR was attained by 70 (65%) children. Genotype was the main predictor of response: G1, 53%; G2/3, 93%; G4, 80%. SVRs were similar in younger and older children. Baseline viral load was the main predictor of response in the G1 cohort. No new safety signals were identified, and adverse events (AEs) were generally mild or moderate in severity. Dose was modified because of AEs in 25% of children; 1 child discontinued because of an AE (thrombocytopenia). No serious AEs related to study drugs were reported., Conclusion: Therapy with PEG-IFN alfa-2b plus RBV in children and adolescents with chronic hepatitis C offers favorable efficacy, reduced injection frequency, and an acceptable safety profile.

Objective: To evaluate the effect of obesity on the presentation and course of disease in patients with gynecological cancers., Study Design: Records of patients with endometrial (n = 1180), cervical (n = 738), and ovarian cancer (n = 824) treated between 1986 and 2005 were reviewed. Body mass index (BMI) was analyzed in relation to tumor stage, tumor grading, and prognosis. Steroid hormone receptor status and growth fraction (MIB1; Ki-67-antigen) of tumors in relation to BMI were analyzed in subgroups with endometrial (n = 183) and advanced ovarian (n = 221) cancers. In the latter subgroup, tumor vascularization (CD31) and expression of bcl-2, c-erb-B2, fibronectin, and tumor markers (CA-125, CA15-3, CEA) were also evaluated. Statistical analyses included bivariate correlation, cross-tabulation, Kaplan-Meier-survival analyses, and multifactorial residual survival analyses., Results: Obese patients with endometrial carcinoma were significantly younger (p < 0.001) and their tumors were less advanced at diagnosis (p = 0.001) and were better differentiated (p = 0.010). In the subgroups, neither steroid hormone receptor status nor MIB1-determined growth fraction correlated with BMI. For both endometrial and cervical carcinomas, a high BMI influenced overall survival favorably (p (endometrial )= 0.004 and p (cervical )= 0.026). In ovarian cancer, there was a trend toward improved survival in more obese patients (p = 0.053). Immunohistochemistry revealed that c-erb-B2 expression was slightly lower in tumors of obese patients (r = -0.142; p = 0.039), but BMI did not influence any other factor., Conclusions: Although obesity increases the incidence of cancer, a high BMI does not seem to adversely influence the prognosis in patients with the mentioned gynecological malignancies.

Aim: To evaluate the prevalence of autoantibodies in chronic hepatitis C virus (HCV)-infected children focusing on thyroid autoimmunity., Methods: We investigated the prevalence of auto-antibodies in 123 chronic HCV-infected children before, during and after monotherapy with interferon-alpha (IFN-alpha) or combined treatment with interferon-alpha or peginterferon-alpha and ribavirin. Besides antibodies against smooth muscle (SMA), nuclei (ANA), and liver/kidney microsomes (LKM), the incidence of anti-thyroid peroxidase antibodies as well as thyroid function parameters (TSH, FT3 and FT4) were determined., Results: We found that 8% of children had autoantibodies before treatment. During treatment, 18% of children were found positive for at least one autoantibody; 15.5% of children developed pathologic thyroid values during IFN-alpha treatment compared to only one child before therapy. Six children had to be substituted while developing laboratory signs of hypothyroidism., Conclusion: Our data indicate a strong correlation between interferon-alpha treatment and autoimmune phenomena, notably the emergence of thyroid antibodies. The fact that some children required hormone replacement underlines the need of close monitoring in particularly those who respond to therapy and have to be treated for more than 6 mo.

Peginterferon plus ribavirin is standard therapy for adults with chronic hepatitis C. As no data are available for children, the aim of the study was to evaluate the efficacy and tolerability of peginterferon alfa-2b in combination with ribavirin in chronically infected children. Genotypes, alanine aminotransferase levels, and different routes of viral transmission were considered. In an open-labeled, uncontrolled pilot study, 62 children and adolescents (range, 2-17 years) were treated with subcutaneous peginterferon alfa-2b at a dose of 1.5 microg/kg body weight once per week plus oral ribavirin (15 mg/kg x day) for 48 weeks. Sixty-one patients completed the study. Twenty-three children discontinued therapy after 6 months according to study protocol. Sustained viral response was documented in 22 (47.8%)of 46 patients with genotype 1, in 13 (100%) of 13 with genotype 2 or 3, in 1 of 2 with genotype 4, in 19 (70.4%) of 27 children with parenteral, in 12 (48%) of 25 with vertical, and in 5 of 9 with unknown route of infection. Overall, treatment was well tolerated. Nevertheless, some side effects were present in all treated patients. Eighty-three percent had leucopenia, but only 3 individuals required dose reduction and 10.3% developed thyroid autoantibodies and thyroid dysfunction. In conclusion, combination treatment of peginterferon alfa-2b with ribavirin showed encouraging results and was well tolerated in children and adolescents with chronic hepatitis C. Weekly dosing of peginterferon alfa-2b is a considerable advance for this age group. The treatment is not approved for children. Further controlled trials are needed.

Physicians represent the main providers of unconventional cancer therapies (UCT) in Germany. However, little is known about providers' characteristics, as well as their attitudes towards UCT. 833 questionnaires on this topic answered by general practitioners and hospital physicians were analysed. Providers differed significantly from non-providers with respect to gender (male>female, i.e. more male providers), age (older>younger), amount of subjective knowledge about UCT, place of work (office>hospital>university clinic), greater wish for coverage of UCT costs, the belief in future positive trends concerning UCT, the recognition of patients' demand for UCT, the number of patients seen per month and medical specialty (GPs>oncologists and radiation oncologists). UCT were not considered to be highly effective, but estimations varied considerably. Further investigations in this area, better education about UCT, training in coping strategies with the fate of cancer patients, and reasonable complementary treatments appear to be of the utmost importance.

Aims: The study investigated factors related to the expectations and wishes concerning delivery of expectant parents., Methods: A self-administered questionnaire on the relevant aspects of delivery was developed, pre-tested, and administered to 545 expectant mothers (n = 336) and fathers (n = 209) attending open house informational events at 3 hospitals around Giessen, Germany., Results: Response rate was 96.3%. Three major areas of interest were identified and converted into scales: "management and obstetrical equipment" (ME; alpha = 0.81), "medical standards" (MS; alpha = 0.82), and "hospital conveniences" (HC; alpha = 0.78). Preferences of participants were influenced by age, gender and parity, as well as by different levels of state- and trait-anxiety. Expectant fathers focused more on HC of the hospital whereas ME, as well as MS, were more important to pregnant women, especially older women from rural areas with high state and/or trait anxiety (p < or = 0.05). However, MS were also found to be important for younger, nulliparous women with at risk pregnancy. Parents of high-risk pregnancies did not emphasize their wishes for ME (p < or = 0.05)., Conclusion: Fashionable obstetrical equipment of delivery rooms, high medical standards, the reputation of the hospital, and certain conveniences are important issues for expectant parents. However, their importance varies with the above mentioned factors.

Objective: Are there differences in self-concept and body image in patients with cancer recurrence in comparison to patients with complete remission? What impact has cancer recurrence on use, users and non-users of unconventional cancer therapies?, Patients and Methods: One hundred and nine patients with no evidence of disease after gynaecological cancer and sixty-one patients with recurrent disease were analysed for self-concept with the Frankfurter Selbstkonzeptskalen and body image with the Frankfurter Körperkonzeptskalen. Use and motivation for unconventional therapies was assessed with a questionnaire., Results: With respect to frequency of use and expected benefits of unconventional therapies no differences were observed between the groups. However, cancer recurrence was found to induce considerable changes of self-concept and body image, some indicating even positive changes due to cancer recurrence., Conclusion: It may be beneficial to consider body therapy and psychotherapy as a mean to improve body image and self-esteem in cases with cancer recurrence.

Mastectomies will remain a treatment alternative for breast cancer in spite of efforts to perform more breast-conserving treatment. Restoration of body symmetry may then be an important issue, which can be achieved by surgical breast reconstruction or with an epicutaneous breast prosthesis. A new improved system has recently been developed, which is self-adhesive to the thorax wall. In this study we investigated the advantages and disadvantages of the new system. The body image of 55 patients after unilateral mastectomy was assessed before they entered the study and after approximately 6 months of experience with the system. The "Frankfurter Körperkonzeptskalen" plus additional questions concerning problems after mastectomy and the handling of the new breast form were used for the assessment. About 50% of the patients had problems with the adhesiveness of the breast form, which remains a problem to be solved. Patients who suffered badly from mastectomy, have a smooth and plane mastectomy scar, and who were not suffering from hot flushes, which can impair the adhesiveness of the prosthesis, were more likely to profit from the new self-supporting breast forms. Significant differences were observed in the scales "self-acceptance of the body", acceptance of the body by others" for the subsets of patients mentioned above. The differences were less pronounced in patients who were already familiar with another type of epicutaneous breast form, which is attached to an adhesive plate on the thorax wall by nylon touch and close fasteners. Most (90.7%) of the patients would recommend this new type of breast prosthesis for other patients with mastectomy. The concept of self-supporting breast forms is an improvement with respect to social and psychological rehabilitation. According to the manufacturer, the problem with adhesion has meanwhile been solved.