Rectum separation in patients with cervical cancer for treatment planning in primary chemo-radiation

PURPOSE: To proof feasibility of hydrogel application in patients with advanced cervical cancer undergoing chemo-radiation in order to reduce rectal toxicity from external beam radiation as well as brachytherapy. MATERIAL AND METHODS: Under transrectal sonographic guidance five patients with proven cervical cancer underwent hydro gel (20 cc) instillation into the tip of rectovaginal septum adherent to posterior part of the visible cervical tumor. Five days after this procedure all patients underwent T2 weighted transversal and sagittal MRI for brachytherapy planning. MRI protocol included T2 weighted fast spin echo (FSE) imaging in sagittal, coronal and para-axial orientation using an 1.5 Tesla MRI. Separation of anterior rectal wall and cervix was documented. RESULTS: Hydrogel application was uneventful in all patients and no toxicity was reported. Separation ranged from 7 to 26 mm in width (median 10 mm). The length of the separation varied between 18 and 38 mm (median 32 mm). In all patients displacement was seen in the posterior vaginal fornix, and/or at the deepest part of uterine cervix depending on the extension of the cul-de-sac in correlation to the posterior wall of the uterus. In patients with bulky tumor and/or deep (vaginal) extend of peritoneal cavity tumour was seen mainly cranial from the rectovaginal space and therefore above the hydrogeI application. Only in the extra-peritoneal (lower) part of the cervix a good separation could be achieved between the rectum and cervix. CONCLUSION: Hydrgel instillation in patients with cervial cancer undergoing chemoradiation is safe and feasible. Because of the loose tissue of the cul-de-sac and its intra- and extraperitoneal part, hydrogel instillation of 20 cc did not result in a sufficient separation of the cervix from anterior wall

Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study

Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity

Die Bedeutung der urodynamisch gemessenen Blasenkapazität und der anhand sonographischer Parameter bestimmten Hypermobilität der Urethra im Kontext von Stress- und Dranginkontinenz sowie deren Mischform bei Frauen

Almost every forth woman is suffering from urinary incontinence. Most frequent types of urinary incontinence are stress urinary incontinence (SUI), over active bladder (OAB) and mixed urinary incontinence (MUI). Beside medical history and sonography, urodynamic testing is commonly used to differentiate between these forms of urinary incontinence. During urodynamic testing the bladder capacity is measured routinely. A small bladder capacity has already been described in patients with over active bladder. Neither in stress urinary incontinence nor in mixed urinary incontinence the meaning of bladder capacity has been analyzed. In this trial the evaluation of a possible relationship between bladder capacity and the type of urinary incontinence was the point of interest. Therefore three groups of women with urinary incontinence were formed, in detail stress urinary incontinence, over active bladder and mixed urinary incontinence. Additionally a continent control group was examined in order to verify the results. As already known from current literature smallest bladder capacity was found in patients with over active bladder. Patients suffering from stress urinary incontinence showed a significantly higher bladder capacity than patients with over active bladder. This mismatch in bladder capacity could be explained with small bladders in the OAB group but could also be a hint for large bladder capacities in patients with SUI. Though these patients presented the largest bladder capacity, a significant difference to the control group was not obvious. Probably a certain bias was created by the control group being continent but showing possible risk factors for SUI in their patient history. Another significant difference was apparent between stress and mixed urinary incontinence. A possible explanation would be that the component of overactivity had a stronger influence than stress component. As urodynamic testing is an expensive and invasive technique, there is desire to establish less invasive diagnostics like perineal sonography. Different sonographic markers for hypermobility of the urethra were measured in this trial and a comparison between the four groups was carried out including correlation analysis of bladder capacity and the sonographic findings. Finally no correlation was obvious. In consequence urodynamic testing so far remains the gold standard for diagnostic in urinary incontinence as it reveals not only morphologic aberrations but also functional changes

Music engagement as a resource for health and well-being: an investigation of psychological and psychobiological correlates in clinical and non-clinical samples

To maintain and improve health and well-being, human beings have naturally turned to music for thousands of years. Nowadays, music is an essential part of everyday life, though the engagement with music can occur in a multitude of ways and contexts. Correspondingly, researchers have become increasingly interested in exploring the health and well-being benefits of music engagement in the domains of music therapy and music medicine, music education, community music, and everyday uses of music. Since the findings from these different domains are rarely integrated, the aim of the present thesis was to investigate the impact of music engagement on psychological and psychobiological aspects of health and well-being in clinical settings (music therapy) and non-clinical settings (everyday music engagement) and to discuss their potential similarities and differences. Therefore, a daily diary study, a meta-analysis, and a randomized controlled trial in different settings of music engagement were conducted. In a non-clinical setting, the daily diary study with hobby musicians (Manuscript 1) showed that autonomous motivation to engage in music making predicted higher affective well-being and life satisfaction. Further, results suggested flow experiences as a mediating mechanism. Regarding a clinical setting, the aim of the systematic review and meta-analysis in Manuscript 2 was to gain a comprehensive overview of the impact of music therapy in oncology on health and well-being. Findings revealed beneficial effects on psychological well-being, quality of life, and physical symptom distress, while the frequency and type of music therapy moderated the effect on psychological well-being. To gain more thorough insights into the palliative care setting, a randomized controlled trial was conducted to evaluate a newly developed biographical music therapy showing beneficial effects on psychospiritual outcomes and treatment satisfaction compared to a relaxation intervention (Manuscript 3). Though there were no treatment effects on psychobiological outcomes, both the experimental and control group showed a significant reduction of cortisol and mean heart rate over time (Manuscript 4). As one of the few works combining research and theories of music psychology and music therapy, the discussion of these exemplary findings outlined similarities of music engagement in clinical and non-clinical settings in terms of health and well-being related study outcomes as well as possible underlying mechanisms such as flow experiences and psychobiological stress reduction. Further, findings also indicated differences in terms of the motivation to engage with music, the type of music engagement, and the presence of a therapeutic relationship. Nonetheless, a joint agenda of these disciplines may have highly relevant implications for both research and practice in prevention and health care with regard to improving the quality of studies and consolidating the role of music engagement as a resource for health and well-being in communities and public systems

The Internal Dynamics of Fibrinogen and Its Implications for Coagulation and Adsorption.

Fibrinogen is a serum multi-chain protein which, when activated, aggregates to form fibrin, one of the main components of a blood clot. Fibrinolysis controls blood clot dissolution through the action of the enzyme plasmin, which cleaves fibrin at specific locations. Although the main biochemical factors involved in fibrin formation and lysis have been identified, a clear mechanistic picture of how these processes take place is not available yet. This picture would be instrumental, for example, for the design of improved thrombolytic or anti-haemorrhagic strategies, as well as, materials with improved biocompatibility. Here, we present extensive molecular dynamics simulations of fibrinogen which reveal large bending motions centered at a hinge point in the coiled-coil regions of the molecule. This feature, likely conserved across vertebrates according to our analysis, suggests an explanation for the mechanism of exposure to lysis of the plasmin cleavage sites on fibrinogen coiled-coil region. It also explains the conformational variability of fibrinogen observed during its adsorption on inorganic surfaces and it is supposed to play a major role in the determination of the hydrodynamic properties of fibrinogen. In addition the simulations suggest how the dynamics of the D region of fibrinogen may contribute to the allosteric regulation of the blood coagulation cascade through a dynamic coupling between the a- and b-holes, important for fibrin polymerization, and the integrin binding site P1