[Current situation of electronic medical records in ophthalmological departments in Germany]. / Status der elektronischen Dokumentation in ophthalmologischen Hauptabteilungen in Deutschland.

BACKGROUND: Electronic medical records are required in ophthalmology clinics to be integrated into digital care networks and efficient clinical registry databases. AIM OF THE WORK: To assess the prevalence and methods of electronic medical recordkeeping in inpatient ophthalmological care in Germany. MATERIAL AND METHODS: An online questionnaire was sent to all German university eye hospitals and ophthalmology departments in June 2021. It included 13 open and closed option questions concerning current practices of digital recordkeeping, including the structure of data storage and the recording of billing-relevant codes in the departments. RESULTS: A total of 44 (44%) out of 100 clinics responded. Patient documentation was completely digital in 15 (34%) clinics and partly digital and paper-based in the remaining 29 (66%). A total of 16 different constellations of documentation programs were specified. The most frequently used programs were Orbis (27%) (Dedalus HealthCare, Bonn, Germany), FIDUS (18%) (Arztservice Wente, Darmstadt, Germany), and SAP/i.s.h.med (16%) (SAP Deutschland, Walldorf, Germany; Cerner Deutschland, Berlin, Germany) and 3 clinics indicated primary use of paper records. Structured documentation of findings was performed in 61% of the departments, while 23% used a semistructured manner and 15% used a nonstructured format. Electronic documents are stored as DICOM (Digital Imaging and Communications in Medicine) documents 20% of the clinics and as PDF (Portable Document Format) files in 34% of the clinics while 23% store scanned printouts. DISCUSSION: Methods of medical record keeping in German eye clinics are heterogeneous, with paper-based documentation continuing to play an important role. This, as well as the high number of different electronic medical record software pose important challenges in terms of interoperability and secondary use of clinical data.

[Experiences of aggression and violence against ophthalmologists]. / Erfahrungen von Aggression und Gewalt gegen Augenärztinnen und Augenärzte.

BACKGROUND: The media have reported an increased willingness of patients and relatives to use violence against medical personnel. So far a few studies have been carried out on this topic and the data situation is correspondingly weak. Ophthalmologists in particular have close contact with patients at the slit lamp and are often alone with patients. METHODS: A questionnaire was developed based on the perception of prevalence of aggression scale (POPAS) questionnaire and the survey on aggression and violence among general practitioners. In autumn 2018, all members of the German Ophthalmological Society (DOG) and the Professional Association of Ophthalmologists (BVA) received an invitation by e­mail to complete the questionnaire online. RESULTS: Of the 9411 ophthalmologists contacted a total of 1508 (age 49 ± 12 years) took part in the survey (16%). Of the respondents 806 (53.7%) were female and 1139 (75.5%) participants worked in practices. A total of 1264 (83.3%) ophthalmologists had experienced aggression/violence in their work, 986 (65%) respondents had already experienced verbal assaults without threats, 363 (24.1%) doctors reported experiences with threats of physical violence and 30 (2%) participants had received medical treatment for severe physical violence. Sexual intimidation/harassment was affirmed by 322 (21.4%) of respondents, of whom 243 (75.5%) were female and 533 (47.9%) doctors felt that aggressive/violent behavior had increased in the last 5 years. CONCLUSION: The high number of participants indicates the high relevance of the topic. The survey produced astonishing results, which should lead to further discussion and action to improve the safety of employees.

Complementary and alternative medicine and musculoskeletal pain in the first year of adjuvant aromatase inhibitor treatment in early breast cancer patients.

BACKGROUND: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. PATIENTS AND METHODS: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. RESULTS: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. CONCLUSIONS: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.

[TILGen study-immunological targets in patients with breast cancer : Influence of tumor-infiltrating lymphocytes]. / TILGen-Studie ­ Immunologische Angriffspunkte bei Patientinnen mit Brustkrebs : Einfluss der tumorinfiltrierenden Lymphozyten.

BACKGROUND: The interaction of our immune system with breast cancer (BC) cells prompted the investigation of tumor-infiltrating lymphocytes (TILs) and targeted, tumor antigen-specific immunotherapy. OBJECTIVES: Correlation between TILs and pathological complete response (pCR) after neoadjuvant systemic therapy (NACT). Tumor-specific antigens (TSAs) in HER2+ and triple negative BC and establishment of TSA-specific therapies within the interdisciplinary TILGen study. METHODS: Illustration of the TILGen study design. Assessment of TILs and correlation with pCR within this BC study. RESULTS: pCR was achieved in 38.4% (56/146) and associated with estrogen receptor/progesterone receptor negative (ER-/PR-) and HER2+ tumors. Lymphocytic predominant BC (LPBC) was found in 16.4% (24/146), particularly in ER-/PR- (ER-: 27.3% vs. ER+: 9.9%, PR-: 22.3% vs. PR+: 8.2%), large, and poorly differentiated BC. TILs were significantly correlated with pCR in multivariate analysis. In LPBC, pCR was achieved in 66.7%, whereas it was 32.8% in non-LPBC. CONCLUSIONS: First results confirm the influence of the human immune system on the response to NACT in HER2+ and triple negative BC. TSA-specific immunotherapy might improve the outcome in BC patients but there is an urgent need for comprehensive studies to further investigate this issue.

Maternal stress during pregnancy induces depressive-like behavior only in female offspring and correlates to their hippocampal Avp and Oxt receptor expression.

The majority of studies examining the consequences of prenatal stress in rodent models analyze pups having been raised by their biological mother, i.e. the female which experienced stress during her pregnancy. To test whether pregnancy stress changes maternal behavior and thereby - in addition to stress exposure in utero - influences behavior and brain function of offspring, we implemented a fostering model, in which mouse pups that were not stressed in utero, are raised by dams which were exposed to stress during their pregnancy. We found that dams, which were stressed during pregnancy (PS foster dams), unexpectedly displayed slightly more active and passive light time nursing compared to unstressed dams (CON foster dams). Adult male offspring which were raised by a PS foster dam showed significantly less anxiety-like behavior compared to males raised by a CON foster dam, whereas adult female offspring which were raised by PS foster dams displayed increased depressive-like behavior as a tendency. Since the arginine vasopressin receptor 1a (AvpR1a) and the structurally related oxytocin receptor (OxtR) are both closely related to stress-responsiveness, anxiety and depression, mRNA expression of these genes were assessed in the hippocampus of adult male and female offspring. No significant differences in mRNA expression of both receptor types were observed, however, in female offspring of PS foster dams maternal licking/grooming correlated positively with AvpR1a and negatively with OxtR mRNA expression. These findings indicate that stress during pregnancy does not reduce, but slightly increase maternal behavior, which might lead to sex-specific behavioral outcomes and changes in hippocampal AvpR1a and OxtR mRNA expression in adult offspring.

Ankyrin-3 as a molecular marker of early-life stress and vulnerability to psychiatric disorders.

Exposure to early-life stress (ELS) may heighten the risk for psychopathology at adulthood. Here, in order to identify common genes that may keep the memory of ELS through changes in their methylation status, we intersected methylome analyses performed in different tissues and time points in rats, non-human primates and humans, all characterized by ELS. We identified Ankyrin-3 (Ank3), a scaffolding protein with a strong genetic association for psychiatric disorders, as a gene persistently affected by stress exposure. In rats, Ank3 methylation and mRNA changes displayed a specific temporal profile during the postnatal development. Moreover, exposure to prenatal stress altered the interaction of ankyrin-G, the protein encoded by Ank3 enriched in the post-synaptic compartment, with PSD95. Notably, to model in humans a gene by early stress interplay on brain phenotypes during cognitive performance, we demonstrated an interaction between functional variation in Ank3 gene and obstetric complications on working memory in healthy adult subjects. Our data suggest that alterations of Ank3 expression and function may contribute to the effects of ELS on the development of psychiatric disorders.

Indications and Route of Hysterectomy for Benign Diseases. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry No. 015/070, April 2015)

Background: Official guideline "indications and methods of hysterectomy" to assign indications for the different methods published and coordinated by the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (OEGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). Besides vaginal and abdominal hysterectomy, three additional techniques have been implemented due to the introduction of laparoscopy. Organ-sparing alternatives were also integrated. Methods: The guideline group consisted of 26 experts from Germany, Austria and Switzerland. Recommendations were developed using a structured consensus process and independent moderation. A systematic literature search and quality appraisal of benefits and harms of the therapeutic alternatives for symptomatic fibroids, dysfunctional bleeding and adenomyosis was done through MEDLINE up to 6/2014 focusing on systematic reviews and meta-analysis. Results: All types of hysterectomy led in studies to high rates of patient satisfaction. If possible, vaginal instead of abdominal hysterectomy should preferably be done. If a vaginal hysterectomy is not feasible, the possibility of a laparoscopic hysterectomy should be considered. An abdominal hysterectomy should only be done with a special indication. Organ-sparing interventions also led to high patient satisfaction rates, but contain the risk of symptom recurrence. Conclusion: As an aim, patients should be enabled to choose that therapeutic intervention for their benign disease of the uterus that convenes best to them and their personal life situation.

Senology in Gynaecology Specialist Training: a Baseline Survey from 2014.

Introduction: Qualified training in senology is essential for maintaining adequate, high quality patient care. In order to meet the needs of doctors in training and those of the medical infrastructure it is necessary to assess the quality of training regularly, to enable its adaption and optimisation. Methods: We developed a comprehensive, 10 item online questionnaire to assess the quality of specialised training in senology. This questionnaire was sent to 4000 speciality trainees and young specialists countrywide via the DGGG newsletter and was accessible for over four weeks. Results: 111 obstetrics and gynaecology speciality trainees participated in this national survey, 79 % of whom were female. 33 % of participants were working at university hospitals, 29 % at hospitals offering maximal level care without an associated medical faculty, 37 % at hospitals offering primary and secondary level care and 2 % at gynaecology practices. 25 % of participants could imagine working in the field of senology in future. On average the current perception of general specialist training was satisfactory. Specialist trainees at university hospitals rated training in senology highest (score: 2.95) compared to those at other hospitals. A fixed rotation through a breast centre offering comprehensive advanced training was seen as a potential improvement to senology training. Conclusions: This is the first survey of specialised training in senology to be conducted in Germany. Results showed that there is significant potential for young doctors to enter the speciality in future. There are also significant differences in the perceived quality of senology training between training facilities. This survey aimed to determine the quality of specialised training at senology centres and hopes to contribute to a sustainable improvement in training. The intention is to continue to make senology attractive to gynaecologists and to ensure well-grounded training.

Conserved Hypothalamic c-Fos Activation Pattern Induced by the mGlu5 Receptor Antagonist MPEP during Peri-pubertal Development in Mice.

INTRODUCTION: 2-Methyl-6-(phenylethynyl)pyridine (MPEP) is a selective mGlu5 receptor (mGluR5) antagonist intensively studied as potential novel anxiolytic drug. In the adult, MPEP activates stress-related areas, including the paraventricular nucleus of the hypothalamus (PVNh). However, it is unknown if MPEP targets similar structures in the juvenile brain as well. METHODS: Here we examined by immunohistochemical methods the induction pattern of the neuronal activity marker c-Fos by MPEP at peri-pubertal stages (postnatal day P16, P24, P32 and P40) in C57BL6/N mice. RESULTS: Despite the previously reported sharply diminished hypothalamic mGluR5 expression during postnatal development, we found a highly conserved PVNh activation by MPEP together with c-Fos expression in the extended amygdala. Interestingly, MPEP also robustly activated the paraventricular nucleus of the thalamus (PVT) and suprachiasmatic nucleus (SCN), regions associated with the modulation of circadian rhythms. DISCUSSION: These results indicate a conserved activation pattern induced by MPEP in the young vs. adult brain especially in brain areas regulating stress and circadian rhythms and may be of importance regarding the effect of mGluR5 antagonists in the treatment of mood disorders during juvenile development.

Morc1 knockout evokes a depression-like phenotype in mice.

Morc1 gene has recently been identified by a DNA methylation and genome-wide association study as a candidate gene for major depressive disorder related to early life stress in rodents, primates and humans. So far, no transgenic animal model has been established to validate these findings on a behavioral level. In the present study, we examined the effects of a Morc1 loss of function mutation in female C57BL/6N mice on behavioral correlates of mood disorders like the Forced Swim Test, the Learned Helplessness Paradigm, O-Maze and Dark-Light-Box. We could show that Morc1(-/-) mice display increased depressive-like behavior whereas no behavioral abnormalities regarding locomotor activity or anxiety-like behavior were detectable. CORT plasma levels did not differ significantly between Morc1(-/-) mice and their wildtype littermates, yet - surprisingly - total Bdnf mRNA-levels in the hippocampus were up-regulated in Morc1(-/-) animals. Although further work would be clarifying, Morc1(-/-) mice seem to be a promising epigenetically validated mouse model for depression associated with early life stress.

The scent of stress: environmental challenge in the peripartum environment of mice affects emotional behaviours of the adult offspring in a sex-specific manner.

Early adverse experiences are known to influence the risk of developing psychiatric disorders later. To shed further light on the development of laboratory mice, we systematically examined the influence of a prenatal or postnatal olfactory stressor, namely unfamiliar male mouse faeces, presented to pregnant or nursing mouse dams. Maternal and offspring behaviours were then examined. Maternal behaviours relative to controls revealed changes in nest building by the pregnant dams exposed to the unfamiliar faeces. There were no differences among groups on pup retrieval or exploration by the dams. Behavioural phenotyping of male and female offspring as adults included measures of exploration, anxiety, social and depressive-like behaviours. Additionally, serum corticosterone was assessed as a marker of physiological stress response. Group differences were dependent on the sex of the adult offspring. Males raised by dams that were stressed during pregnancy presented elevated emotionality as indicated by increased numbers of faecal boluses in the open field paradigm. Consistent with the effects of prenatal stress on the males only the prenatally stressed females had higher body weights than their respective controls. Indeed, males in both experimental groups had higher circulating corticosterone levels. By contrast, female offspring of dams exposed to the olfactory stressor after parturition were more anxious in the O-maze as indicated by increased latencies in entering the exposed areas of the maze. These findings emphasize the necessity for researchers to consider the pre- and postnatal environments, even of mice with almost identical genetic backgrounds, in designing experiments and interpreting their data.

Minocycline does not evoke anxiolytic and antidepressant-like effects in C57BL/6 mice.

Minocycline is a broad-spectrum tetracycline antibiotic with multiple actions, including anti-inflammatory and neuroprotective effects, that was proposed as novel treatment for several psychiatric disorders including schizophrenia and depression. However, there are contradictory results regarding antidepressant effects of minocycline in rodent models. Additionally, the possible anxiolytic effect of minocycline is still poorly investigated. Therefore, we aimed to clarify in the present study the influence of minocycline on behavioral correlates of mood disorders in standard tests for depression and anxiety, the Porsolt Forced Swim Test (FST), Elevated O-Maze, Dark-Light Box Test and Openfield Test in adult C57BL/6 mice. We found, unexpectedly, that mice treated with minocycline (20-40mg/kg, i.p.) did not display antidepressant- or anxiolytic-like behavioral changes in contrast to mice treated with diazepam (0.5mg/kg, anxiety tests) or imipramine (20mg/kg, depressive-like behavior). These results are relevant for future studies, considering that C57BL/6 mice, the most widely used strain in pharmacological and genetic animal models, did not react as expected to the treatment regime applied.

Sarcoma of the Uterus. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015/074, August 2015).

Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Due to their rarity and their heterogeneous histopathology uterine sarcomas remain challenging tumors to manage and need a multidisciplinary approach. To our knowledge so far there is no evidence-based guideline on the appropiate management of these heterogeneous tumors. Methods: This S2k-guideline is the work of an representative committee of experts from a variety of different professions who were commissioned by the DGGG to carry out a systematic literature review of uterine sarcoma. Members of the participating scientific societies developed a structured consensus in a formal procedure. Recommendations: 1. The incidence and histopathologic classification of uterine sarcoma. 2. The clinical manifestations, diagnosis and staging of uterine sarcoma. 3. The management of leiomyosarcoma. 4. The management of endometrial stromal sarcoma and undifferentiated uterine sarcoma. 5. The management of adenosarcoma as well as carcinosarcomas. 6. The management of morcellated uterine sarcoma.

Surgical Methods for the Treatment of Uterine Fibroids - Risk of Uterine Sarcoma and Problems of Morcellation: Position Paper of the DGGG.

The appropriate surgical technique to treat patients with uterine fibroids is still a matter of debate as is the potential risk of incorrect treatment if histological examination detects a uterine sarcoma instead of uterine fibroids. The published epidemiology for uterine sarcoma is set against the incidence of accidental findings during surgery for uterine fibroids. International comments on this topic are discussed and are incorporated into the assessment by the German Society for Gynecology and Obstetrics (DGGG). The ICD-O-3 version of 2003 was used for the anatomical and topographical coding of uterine sarcomas, and the "Operations- und Prozedurenschlüssel" (OPS) 2014, the German standard for process codes and interventions, was used to determine surgical extirpation methods. Categorical qualifiers were defined to analyze the data provided by the Robert Koch Institute (RKI), the German Federal Bureau of Statistics (DESTATIS; Hospital and Causes of Death Statistics), the population-based Cancer Register of Bavaria. A systematic search was done of the MEDLINE database and the Cochrane collaboration, covering the period from 1966 until November 2014. The incidence of uterine sarcoma and uterine fibroids in uterine surgery was compared to the literature and with the different registries. The incidence of uterine sarcoma in 2010, standardized for age, was 1.53 for Bavaria, or 1.30 for every 100 000 women, respectively, averaged for the years 2002-2011, and 1.30 for every 100 000 women in Germany. The mean incidence collated from various surveys was 2.02 for every 100 000 women (0.35-7.02; standard deviation 2.01). The numbers of inpatient surgical procedures such as myoma enucleation, morcellation, hysterectomy or cervical stump removal to treat the indication "uterine myoma" have steadily declined in Germany across all age groups (an absolute decrease of 17 % in 2012 compared to 2007). There has been a shift in the preferred method of surgical access from an abdominal/vaginal approach to endoscopic or endoscopically assisted procedures to treat uterine fibroids, with the use of morcellation increasing by almost 11 000 coded procedures in 2012. Based on international statements (AAGL, ACOG, ESGE, FDA, SGO) on the risk of uterine sarcoma as an coincidental finding during uterine fibroid surgery and the associated risk of a deterioration of prognosis (in the case of morcellation procedures), this overview presents the opinion of the DGGG in the form of four Statements, five Recommendation and four Demands.

Immobilization stress sensitizes rat dorsal horn neurons having input from the low back.

BACKGROUND: Stress is known to promote several forms of muscle pain including non-specific low back pain. However, the question if stress alone activates nociceptive central neurons has not been studied systematically. Here, we investigated the influence of repeated immobilization stress on dorsal horn neurons and behaviour in the rat. METHODS: The stress consisted of immobilization in a narrow tube for 1 h on 12 days. Single dorsal horn neurons were recorded with microelectrodes introduced into the spinal segment L2. In this segment, about 14% of the neurons responded to mechanical stimulation of the subcutaneous soft tissues of the low back in naïve rats. The neurons often behaved like wide dynamic range cells in that they had a low mechanical threshold and showed graded responses to noxious stimuli. RESULTS: The stress-induced changes in neuronal response behaviour were (1) appearance of new receptive fields in the deep tissues of the hindlimb, (2) increased input from deep soft tissues, but unchanged input from the skin and (3) significant increase in resting activity. Surprisingly, the pressure-pain threshold of the low back remained unchanged, although dorsal horn neurons were sensitized. In the open field test, the rats showed signs of increased anxiety. CONCLUSIONS: This study shows that stress alone is sufficient to sensitize dorsal horn neurons. The data may explain the enhanced pain low back patients report when they are under stress. The increased resting discharge may lead to spontaneous pain.

Implications of p75NTR for dentate gyrus morphology and hippocampus-related behavior revisited.

The pan-neurotrophin receptor p75NTR is expressed in the adult brain in a discrete pattern. Although numerous studies have addressed its implications for hippocampal functions, the generated sets of data are surprisingly conflicting. We have therefore set out to re-investigate the impact of a deletion of the full-length p75NTR receptor on several parameters of the dentate gyrus (DG), including neurogenesis and hippocampus-related behavior by using p75NTR(ExIII) knockout mice. Moreover, we investigated further parameters of the DG (cholinergic innervation, dendritic spines). In addition, we analyzed on the morphological level the impact of aging by comparing adult and aged p75NTR(ExIII) mice and their age-matched littermates. Adult (4-6 months old), but not aged (20 months old), p75NTR(ExIII) knockout mice display an enhanced volume of the DG. However, adult neurogenesis within the adult DG was unaffected in both adult and aged p75NTR(ExIII) knockout mice. We could further demonstrate that the change in the volume of the DG was accompanied by an increased cholinergic innervation and increased spine densities of granule cells in adult, but not aged p75NTR deficient mice. These morphological changes in the adult p75NTR deficient mice were accompanied by specific alterations in their behavior, including altered behavior in the Morris water maze test, indicating impairments in spatial memory retention.

Erratum: Sarcoma of the Uterus. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015/074, August 2015).

[This corrects the article DOI: 10.1055/s-0035-1558120.].

MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD.

Early life stress (ELS) is associated with increased vulnerability for diseases in later life, including psychiatric disorders. Animal models and human studies suggest that this effect is mediated by epigenetic mechanisms. In humans, epigenetic studies to investigate the influence of ELS on psychiatric phenotypes are limited by the inaccessibility of living brain tissue. Due to the tissue-specific nature of epigenetic signatures, it is impossible to determine whether ELS induced epigenetic changes in accessible peripheral cells, for example, blood lymphocytes, reflect epigenetic changes in the brain. To overcome these limitations, we applied a cross-species approach involving: (i) the analysis of CD34+ cells from human cord blood; (ii) the examination of blood-derived CD3+ T cells of newborn and adolescent nonhuman primates (Macaca mulatta); and (iii) the investigation of the prefrontal cortex of adult rats. Several regions in MORC1 (MORC family CW-type zinc finger 1; previously known as: microrchidia (mouse) homolog) were differentially methylated in response to ELS in CD34+ cells and CD3+ T cells derived from the blood of human and monkey neonates, as well as in CD3+ T cells derived from the blood of adolescent monkeys and in the prefrontal cortex of adult rats. MORC1 is thus the first identified epigenetic marker of ELS to be present in blood cell progenitors at birth and in the brain in adulthood. Interestingly, a gene-set-based analysis of data from a genome-wide association study of major depressive disorder (MDD) revealed an association of MORC1 with MDD.

DGGG Guidelines Programme: Status Quo - Quo Vadis!

The Guidelines programme of the German Society of Gynaecology and Obstetrics (DGGG) is an executive part of the DGGG Guidelines Commission. It includes in-house planning and organisation of all guidelines as well as representation outside of the DGGG. This article does not concern the development of the guidelines as much as it concerns the planning, organisation, registration, editing and publication of the guidelines in context of the DGGG Guidelines programme. It targets interested parties, especially authors and coordinators of guidelines.