Safety, efficacy and quality of life of the novel vaginal contraceptive ring containing etonogestrel/ethinylestradiol 11.0/3.474 mg after 3 years of "real life" experience.

Combined contraceptive vaginal rings (CVR) are increasingly appreciated due to several beneficial properties like avoidance of the hepatic first-pass effect, a comparatively low dosage of hormones and comfortable use. A further development of the widely used CVR releasing 0.12 mg etonogestrel (ETO) and 0.015 mg ethinylestradiol (EE) per 24 hours has been marketed since 2017. The 11.00/3.474 mg ETO/EE CVR Ornibel® is bioequivalent to the former product but differs in its polymer composition leading to improved stability. Here, results from recent studies on the novel CVR Ornibel® are reviewed including clinical trials on bleeding profile, acceptability, sexual function and other quality of life (QoL) parameters as well as in vitro studies on microbial adhesion to the CVR and the influence of ring rupture on hormone release. Findings are complemented with new data on contraceptive efficacy and safety of the new CVR that were assessed during 3 years of real-life experience.

Prebiotic supplementation over a cold season and during antibiotic treatment specifically modulates the gut microbiota composition of 3-6 year-old children.

Supplementing kindergarten children during a cold season with a prebiotic inulin-type fructans product with shorter and longer fructan chains has been shown to reduce febrile episodes requiring medical attention and to lower the incidence of sinusitis. These beneficial effects may be connected to the specific modulation of children's gut microbiota. By applying quantitative and qualitative microbiota analysis this study aimed at characterising the gut microbiota composition and at exploring effects of prebiotic intervention on the gut microbiota during a 24-weeks intervention and during antibiotic treatment in healthy children. The study was a randomised, placebo-controlled trial with 258 healthy children aged 3 to 6 years consuming 6 g/day prebiotic inulin-type fructans or maltodextrin. During the course of the study, faecal samples were collected and subject to targeted qPCR analysis and phylogenetic profiling by multiplexed high throughput sequencing of the prokaryotic 16S rRNA gene PCR amplicons. The microbiota composition of the cohort could be clustered into three distinct constellations (enterotypes). Prebiotic intake resulted in a selective modulation of the gut microbiota composition. Relative abundance of Bifidobacterium was significantly higher in the prebiotic group (n=104) compared to control group (n=105) and this effect was found for all three enterotypes. Antibiotic administration decreased the relative abundance of Bifidobacterium in both groups. Nonetheless, children of the prebiotic group receiving antibiotic treatment displayed significantly higher levels of Bifidobacterium than children receiving the placebo control. Prebiotic supplementation induced specific changes in the gut microbiota composition of children aged 3 to 6 years. Moreover, it attenuated antibiotic-induced disturbances in the gut microbiota composition as shown by higher relative abundance of bifidobacteria at the end of the antibiotic treatment in the prebiotic group. With the previously reported benefits on immune function, the study contributes to the evidence on the immune-modulating effects of prebiotics through gut microbiota modifications. The study was registered as NCT03241355 ( https://clinicaltrials.gov/show/NCT03241355 ).

[5-Year-Follow-up of the MEmbeR Multicenter Study on Medical-Occupational Rehabilitation]. / 5-Jahres-Follow-Up der multizentrischen Evaluationsstudie zur medizinisch-beruflichen Rehabilitation (MEmbeR).

In Germany, medical-occupational rehabilitation represents an essential link between rehabilitation programs focusing either on medical or occupational rehabilitation. Its main objective is return to work. The current study presents the vocational integration 5 years after medical-occupational rehabilitation and determines possible prognostic factors for long-term occupational integration. To evaluate the effectiveness of medical-occupational rehabilitation, a 5-year-follow-up interview was conducted with participants (n=105) of the multicenter study on medical-occupational rehabilitation (MEmbeR). As a main result, 76% of the participants were still employed 5 years after medical-occupational rehabilitation and the return to work rate was 57%. Prognostic factors for long-term occupational integration could not be identified. However, a low degree of disability, an unrestricted capacity for teamwork as well as an unrestricted ability to judge might be beneficial factors for a successful reintegration. The high amount of participants who returned to work 5 years after medical-occupational rehabilitation, supports the concept of medical-occupational rehabilitation. However, more studies are needed to identify further factors influencing the outcome.

[Relevance of Magnet Resonance Tomography in the Diagnosis and Assessment of Course of Disease in Patients with Multiple Sclerosis]. / Magnetresonanztomografie bei Patienten mit Multipler Sklerose: Relevanz in der Diagnose und Verlaufsbeurteilung.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) with a substantial destructive axonal component that is responsible for the permanent disability accumulating during the course of the disease. Magnetic resonance imaging (MRI) has become the most important method in the diagnosis of MS. The high sensitivity of the MRI permits to detect focal and diffuse inflammatory disease involvement in vivo. In clinical routine the detection and quantification of focal pathology contributes substantially to an early diagnosis of MS. The detection of a substantial lesion load at the beginning of the disease increases the probability of an early conversion to clinically definite MS and the risk of accumulating disability in the first years of the disease. In 2001 this diagnostic and prognostic gain of information at an early stage of the disease resulted in a conceptual shift regarding diagnostic criteria. This concept comprises clinical and MRI criteria. The current 2010 revised criteria follow the concept of substituting a clinical relapse by subclinical MRI activity and allow the diagnosis of MS from one single MRI after the first relapse. This diagnostic approach using MRI allows an early treatment within an appropriate window of treatment opportunity.

[Management of complications in anal and transanal tumor surgery]. / Komplikationsmanagement bei analer und transanaler Tumorchirurgie.

Anal and transanal tumor operations are safe and are associated with a very low morbidity. Perianal and anal lesions as well as low rectal tumors can be excised by direct exposure using an anal retractor. For lesions situated in the middle or upper third of the rectum, special instrumentation, such as transanal endoscopic microsurgery (TEM) and transanal endoscopic operation (TEO) should be used to avoid unnecessary R1 resections. Fatal complications are extremely rare and most complications, such as urinary retention or temporary subfebrile temperatures, are minor. Suture line dehiscences are usually clinically unremarkable. Major complications comprise significant hemorrhage and opening of the peritoneal cavity. The latter must be recognized intraoperatively and can usually be managed by primary suturing. Infections, abscess formation, rectovaginal fistula, injury of the prostate or even urethra are extremely rare complications.

Quercetin decreases high-fat diet induced body weight gain and accumulation of hepatic and circulating lipids in mice.

Dietary flavonoids may protect against cardiovascular diseases (CVD). Increased circulating lipid levels and hepatic lipid accumulation are known risk factors for CVD. The aim of this study was to investigate the effects and underlying molecular mechanisms of the flavonoid quercetin on hepatic lipid metabolism in mice with high-fat diet induced body weight gain and hepatic lipid accumulation. Adult male mice received a 40 energy% high-fat diet without or with supplementation of 0.33 % (w/w) quercetin for 12 weeks. Body weight gain was 29 % lower in quercetin fed mice (p < 0.01), while the energy intake was not significantly different. Quercetin supplementation lowered hepatic lipid accumulation to 29 % of the amount present in the control mice (p < 0.01). (1)H nuclear magnetic resonance serum lipid profiling revealed that the supplementation significantly lowered serum lipid levels. Global gene expression profiling of liver showed that cytochrome P450 2b (Cyp2b) genes, key target genes of the transcription factor constitutive androstane receptor (Car; official symbol Nr1i3), were downregulated. Quercetin decreased high-fat diet induced body weight gain, hepatic lipid accumulation and serum lipid levels. This was accompanied by regulation of cytochrome P450 2b genes in liver, which are possibly under transcriptional control of CAR. The quercetin effects are likely dependent on the fat content of the diet.

Reduced magnetisation transfer ratio in cognitively impaired patients at the very early stage of multiple sclerosis: a prospective, multicenter, cross-sectional study.

OBJECTIVES: Cognitive impairment belongs to the core symptoms in multiple sclerosis (MS) and can already be present at the very early stages of the disease. The present study evaluated cognitive functioning after the first clinical presentation suggestive of MS and brain tissue damage in a non-lesion focused MRI approach by using magnetisation transfer imaging (MTI). SETTING AND PARTICIPANTS: 47 patients (15 men and 32 women; mean age: 31.17 years) after the first clinical event suggestive of MS were recruited in six different MS centres in Germany and underwent a neuropsychological test battery including tests for attention, memory and executive function as well as depression and fatigue. MTI and conventional MRI measures (T1/T2 lesion load) were assessed. In addition, Magnetisation Transfer Ratio (MTR) maps were calculated. Primary outcome measure was the investigation of cognitive dysfunction in very early MS in correlation to MRI data. RESULTS: 55.3% of patients with MS failed at least one test parameter. Specifically, 6% were reduced in working memory, 14.9% in focused attention, 25.5% in figural learning and up to 14.9% in executive function. When the sample was subdivided into cognitively impaired and preserved, MTR scores within the cognitively impaired subgroup were significantly lower compared with the preserved group (t(43)=2.346, p=0.02*). No significant differences between the two groups were found in T2-weighted and T1-weighted lesion volume. CONCLUSIONS: After the first MS-related clinical event, 55.3% of patients showed distinct cognitive deficits. Cognitively impaired patients had significantly lower whole brain MTR, but no differences in focal brain lesion volumes supporting the idea that early cognitive deficits may be related to diffuse loss of brain tissue integrity.

[The MEmbeR Multicenter Study on medical-occupational rehabilitation]. / Multizentrische Evaluationsstudie zur medizinisch-beruflichen Rehabilitation (MEmbeR).

INTRODUCTION: MEmbeR is a prospective multi-center study on medical-occupational rehabilitation in Germany. METHODS: 196 neurological, psychiatric, orthopaedic, and internal medicine patients from 21 rehabilitation centres all across Germany have been enrolled and followed-up for 2 years after discharge. Primary outcome parameter was defined as return to work. Further, the SF-12 and a Mini-ICF-Rating have been used. RESULTS: Mean age was 34.1 (9.9) years, length of stay 150.0 (223.5) days. Prior to occupational rehabilitation, 69.9% were unable to work, 2 years after discharge only 5.6%. Rate of participants seeking a job was reduced from 19.7% to 3.1%. In summary, 78.1% returned to work. Employed participants were younger (32.8 [9.7] vs. 38.5 [9.4] years, p=0.001) and less disabled (Degree of Disablement [GdB]: 20.0 [31.2] vs. 36.1 [33.7], p<0.05). CONCLUSION: The multicenter cohort study MEmbeR provides further knowledge about the outcome of medical-occupational rehabilitation in Germany.

[Transanal endoscopic operation: indications and technique]. / Indikation und Technik der transanal endoskopischen Operation.

Transanal endoscopic operation (TEO) is a minimally invasive treatment option for certain rectal tumors. The TEO procedure has evolved as a new technique from transanal endoscopic microsurgery (TEM) which was developed by G. Buess. Apart from the excision of benign lesions this method can also be applied in patients with low-risk T1 carcinoma if size and localization permit complete resection (R0). Using these strict criteria for patient selection one can expect an excellent oncological outcome. However, it must to be stressed that local excision is always part of the diagnostic work-up and that the definitive histology needs to be appreciated. In cases of unfavorable histology (i.e. high risk or higher T stage) radical salvage resection should be performed. Functional results and quality of life are very good following TEO or TEM procedures, especially when comparing the outcome with that of radical rectal resection or abdominoperineal excision.

Patient-reported quality of life in multiple sclerosis differs between cultures and countries: a cross-sectional Austrian-German-Polish study.

BACKGROUND: Patient-reported quality of life (QOL) is an outcome measure in clinical trials in multiple sclerosis (MS), but translated QOL instruments may affect the actual comparability of data. OBJECTIVES: We aimed to investigate possible differences in QOL in MS between cultures and countries. We employed the Functional Assessment of Multiple Sclerosis (FAMS) Version 4 questionnaire, which is a state-of-the-art QOL instrument. METHODS: Some 484 MS patients from Austria (145), Germany (144), and Poland (195) aged 20-60 years, and stratified for sex and disease severity as measured by the Expanded Disability Status Scale (EDSS) score completed the respective FAMS translation and a socio-demographic questionnaire. RESULTS: Analysis of variance and post-hoc Scheffé-test showed that 64% of the FAMS items were answered significantly differently (p < 0.001) between the three countries. A multivariate regression analysis including all the available disease-related and socio-demographic variables revealed the factors age, EDSS score, employment, social contacts, MS course, and country to be significant predictors of both the total FAMS score and the score for items answered differently between the three countries. CONCLUSIONS: Differences exist in the QOL of MS patients from Austria, Germany, and Poland which seem to lie beyond the impact of disease severity. They appear to be related to culture or other country-specific factors, as country was an independent predictor of differently answered items of the FAMS and thus also of the whole FAMS. QOL instruments should consider this aspect to faithfully reflect subjective information such as patient-reported benefit of treatment in multinational clinical trials.

Three-dimensional analysis of intermediate filament networks using SEM tomography.

We identified tomographic reconstruction of a scanning electron microscopy tilt series recording the secondary electron signal as a well-suited method to generate high-contrast three-dimensional data of intermediate filament (IF) networks in pancreatic cancer cells. Although the tilt series does not strictly conform to the projection requirement of tomographic reconstruction, this approach is possible due to specific properties of the detergent-extracted samples. We introduce an algorithm to extract the graph structure of the IF networks from the tomograms based on image analysis tools. This allows a high-resolution analysis of network morphology, which is known to control the mechanical response of the cells to large-scale deformations. Statistical analysis of the extracted network graphs is used to investigate principles of structural network organization which can be linked to the regulation of cell elasticity.

Bimonthly assessment of magnetization transfer magnetic resonance imaging parameters in multiple sclerosis: a 14-month, multicentre, follow-up study.

This study was performed to assess the temporal evolution of damage within lesions and the normal-appearing white matter, measured using frequent magnetization transfer (MT) MRI, in relapsing-remitting multiple sclerosis (RRMS). The relationship of MT ratio (MTR) changes with measures of lesion burden, and the sample sizes needed to demonstrate a treatment effect on MTR metrics in placebo-controlled MS trials were also investigated. Bimonthly brain conventional and MT MRI scans were acquired from 42 patients with RRMS enrolled in the placebo arm of a 14-month, double-blind trial. Longitudinal MRI changes were evaluated using a random effect linear model accounting for repeated measures, and adjusted for centre effects. The Expanded Disability Status Scale (EDSS) score remained stable over the study period. A weak, but not statistically significant, decrease over time was detected for normal-appearing brain tissue (NABT) average MTR (-0.02% per visit; p = 0.14), and MTR peak height (-0.15 per visit; p = 0.17), while average lesion MTR showed a significant decrease over the study period (-0.07% per visit; p = 0.03). At each visit, all MTR variables were significantly correlated with T2 lesion volume (LV) (average coefficients of correlation ranging from -0.54 to -0.28, and p-values from <0.001 to 0.02). At each visit, NABT average MTR was also significantly correlated with T1-hypointense LV (average coefficient of correlation = -0.57, p < 0.001). The estimation of the sample sizes required to demonstrate a reduction of average lesion MTR (the only parameter with a significant decrease over the follow-up) ranged from 101 to 154 patients to detect a treatment effect of 50% in a 1-year trial with a power of 90%. The steady correlation observed between conventional and MT MRI measures over time supports the hypothesis of axonal degeneration of fibres passing through focal lesions as one of the factors contributing to the overall MS burden.

[Metastasis of an esophageal carcinoma at a PEG site--case report and review of the literature]. / PEG-Implantationsmetastase eines Osophaguskarzinoms--Fallbericht und Literaturübersicht.

We describe the case of a 54-year-old man with a tumour of the proximal esophagus (cT3-4,N1,M0), who underwent percutaneous endoscopic gastrostomy (PEG) for enteral feeding. Primary radiochemotherapy was initiated shortly after PEG insertion. Five months after PEG insertion the patient detected a nodule at the site. The general practitioner diagnosed this nodule as a brotic reaction. Another six weeks later, ulceration that had grown along the PEG probe at the PEG site was observed on gastroscopy. The primary tumour was not visible. Histological examination showed an abdominal wall metastasis of the esophageal cancer. Despite subtotal gastrectomy with en-bloc resection of the tumour, distant metastasis developed. The patient died six months after surgery. About 47 cases of abdominal wall metastases as late complications at the site have been reported until now. The mechanism of tumour spread of PEG site is a subject of controversial discussion. As direct mechanical tumour implantation is the most likely mechanism, an alternative method like operative (laparoscopic) or radiological PEG placement should be considered in cases with advanced, stenotic tumours.

[Cerebral and spinal MRI examination in patients with clinically isolated syndrome and definite multiple sclerosis]. / Zerebrale und spinale MRT-Untersuchung bei Patienten mit klinisch isoliertem Syndrom oder gesicherter Multipler Sklerose.

PURPOSE: Magnetic resonance imaging (MRI) has become a valuable tool for diagnosing and monitoring multiple sclerosis (MS). The high sensitivity for the detection of hyperintense lesions in T 2-weighted scans contributes substantially to diagnosis. The initial lesion number or lesion volume stands for an increased probability of further accumulation of lesion burden, an earlier conversion to clinically definite MS and progression of disability in the next 5 - 15 years. This diagnostic and prognostic information gained from MRI early in the disease course lead in 2001 to a revision of the diagnostic criteria. MATERIALS AND METHODS: For the first time MRI criteria were defined in addition to the clinical and paraclinical criteria using the clinical terms for dissemination with respect to space and time. In particular, the defined MRI criteria are based on lesion number and location, the appearance of new lesions and lesion enhancement using contrast agent. RESULTS: Reliable detection and description of older and new lesions in the disease course by MRI represents subclinical disease activity which can substitute the clinical confirmation of a relapse leading to an earlier diagnosis. This places importance on the assessment of the subclinical disease activity in sequential MR scans requiring a standardized and reproducible approach to minimize variability despite different MR scanners. CONCLUSION: This review provides an updated proposal for the approach and management of cranial and spinal MR scans in patients with MS. We describe the influence of variables which cannot be standardized (scanner, field strength, manufacturer and software) and outline potential pitfalls of clinical MR imaging in MS resulting from a non-standardized approach. This updated proposal for slice positioning, sequences and documentation is a result of a consensus process targeting systematic and standardized use in clinical MR evaluations of MS.

Short-term results of Karydakis flap for pilonidal sinus disease.

BACKGROUND: Because of the higher quality of life that the Karydakis flap provides compared to excision-only treatment, it became a recommended closure technique for pilonidal sinus disease. This study aimed to evaluate whether Karydakis flap technique can be performed in potentially infected tissue if the surrounding cellulitis allows wound closure. METHODS: 188 patients with pilonidal sinus who underwent excision only (n=91, 48%) or the Karydakis-flap technique (n=97, 52%) were evaluated. The results were reviewed according to the degree of wound contamination, and the effects of closure technique were studied in terms of early wound complications and the duration of hospital stay. RESULTS: In the excision-only group, one patient developed a hematoma (1%) and one patient had cellulitis of the surrounding tissue (1%), which resulted in a 2% complication rate this group. In the Karydakis flap group, wound abscesses were observed in 12 patients (12%). Additionally, four patients (4%) had hematomas, two patients had seromas (2%) and three had other complications. For the Karydakis group, the overall complication rate was 21%, significantly higher than that for the excision-only group (p<0.01). In the Karydakis group, no association was found between complications and the degree of contamination (p=0.36). CONCLUSIONS: These data provide evidence that the Karydakis flap technique might be performed even in potentially infected tissue. Although a considerable number of wound-related complications was observed in the Karydakis flap group, the majority of patients had primary healing. Thus, from our viewpoint, the Karydakis flap seems to be a potential alternative to simple excision in infected pilonidal sinus disease.

[Surgical options in the treatment of rectal prolapse: indications, techniques and results]. / Chirurgische Therapieoptionen beim Rektumprolaps--Indikation, Technik und Ergebnisse.

Two different approaches can be distinguished in the surgical treatment of rectal prolapse, i. e. the transabdominal route and the perineal procedures. The following article deals with both operative options with a detailed discussion of the Delorme's operation and the perineal rectosigmoidectomy, also known as the Altemeier procedure for the perineal techniques. Regarding abdominal operations simple rectopexy is compared with operations including bowel resection including minimally invasive approaches. In general, perineal procedures for full-thickness rectal prolapse cause less morbidity compared with abdominal operations. They are especially indicated in the elderly and /or high-risk patients. Recurrences, on the other hand, are usually encountered more often following local techniques as compared with abdominal operations. It can be concluded that perineal as well as abdominal procedures remain important options in the surgical treatment of rectal prolapse and should be part of the armamentarium of colorectal surgeons.