Intratumoral heterogeneity after targeted therapy in murine cancer models with differing degrees of malignancy.

INTRODUCTION: Conventional morphologic and volumetric assessment of treatment response is not suitable for adequately assessing responses to targeted cancer therapy. The aim of this study was to evaluate changes in tumor composition after targeted therapy in murine models of breast cancer with differing degrees of malignancy via non-invasive magnetic resonance imaging (MRI). MATERIALS AND METHODS: Mice bearing highly malignant 4T1 tumors or low malignant 67NR tumors were treated with either a combination of two immune checkpoint inhibitors (ICI, anti-PD1 and anti-CTLA-4) or the multi-tyrosine kinase inhibitor sorafenib, following experiments with macrophage-depleting clodronate-loaded liposomes and vessel-stabilizing angiopoietin-1. Mice were imaged on a 9.4 T small animal MRI system with a multiparametric (mp) protocol, comprising T1 and T2 mapping and diffusion-weighted imaging. Tumors were analyzed ex vivo with histology. RESULTS AND DISCUSSIONS: All treatments led to an increase in non-viable areas, but therapy-induced intratumoral changes differed between the two tumor models and the different targeted treatments. While ICI treatment led to intratumoral hemorrhage, sorafenib treatment mainly induced intratumoral necrosis. Treated 4T1 tumors showed increasing and extensive areas of necrosis, in comparison to 67NR tumors with only small, but also increasing, necrotic areas. After either of the applied treatments, intratumoral heterogeneity, was increased in both tumor models, and confirmed ex vivo by histology. Apparent diffusion coefficient with subsequent histogram analysis proved to be the most sensitive MRI sequence. In conclusion, mp MRI enables to assess dedicated therapy-related intratumoral changes and may serve as a biomarker for treatment response assessment.

Left atrial appendage volume is an independent predictor of atrial arrhythmia recurrence following cryoballoon pulmonary vein isolation in persistent atrial fibrillation.

Purpose: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation in persistent AF (persAF), and cryoballoon PVI emerged as an initial ablation strategy. Symptomatic atrial arrhythmia recurrence following successful PVI in persAF is observed more frequently than in paroxysmal AF. Predictors for arrhythmia recurrence following cryoballoon PVI for persAF are not well described, and the role of left atrial appendage (LAA) anatomy is uncertain. Methods: Patients with symptomatic persAF and pre-procedural cardiac computed tomography angiography (CCTA) images undergoing initial second-generation cryoballoon (CBG2) were enrolled. Left atrial (LA), pulmonary vein (PV) and LAA anatomical data were assessed. Clinical outcome and predictors for atrial arrhythmia recurrence were evaluated by univariate and multivariate regression analysis. Results: From May 2012 to September 2016, 488 consecutive persAF patients underwent CBG2-PVI. CCTA with sufficient quality for measurements was available in 196 (60.4%) patients. Mean age was 65.7 ± 9.5 years. Freedom from arrhythmia was 58.2% after a median follow-up of 19 (13; 29) months. No major complications occurred. Independent predictors for arrhythmia recurrence were LAA volume (HR 1.082; 95% CI, 1.032 to 1.134; p = 0.001) and mitral regurgitation ≥ grade 2 (HR, 2.49; 95% CI 1.207 to 5.126; p = 0.013). LA volumes ≥110.35 ml [sensitivity: 0.81, specificity: 0.40, area under the curve (AUC) = 0.62] and LAA volumes ≥9.75 ml (sensitivity: 0.56, specificity 0.70, AUC = 0.64) were associated with recurrence. LAA-morphology, classified as chicken-wing (21.9%), windsock (52.6%), cactus (10.2%) and cauliflower (15.3%), did not predict outcome (log-rank, p = 0.832). Conclusion: LAA volume and mitral regurgitation were independent predictors for arrhythmia recurrence following cryoballoon ablation in persAF. LA volume was less predictive and correlated with LAA volume. LAA morphology did not predict the clinical outcome. To improve outcomes in persAF ablation, further studies should focus on treatment strategies for persAF patients with large LAA and mitral regurgitation.

Do biometric parameters improve the quality of optic nerve head measurements with spectral domain optical coherence tomography?

BACKGROUND: Spectral domain optical coherence tomography (SD-OCT) is a widely applied non-invasive technique for evaluating optic nerve head parameters. The aim of this study was to evaluate the impact of biometric parameters such as the spherical equivalent (SE) and the anterior corneal curvature (ACC) on the peripapillary retinal nerve fiber layer (pRNFL), Bruch's membrane opening (BMO), and the minimum rim width (MRW) measurements performed by spectral domain optical coherence tomography (SD-OCT) in glaucomatous and healthy eyes. METHODS: In this cross-sectional, case-control prospective pilot study, the glaucoma group consisted of 50 patients with previously diagnosed and treated glaucoma and one healthy group of 50 subjects. Two consecutive examinations of pRNFL, BMO, and MRW with SD-OCT for every patient were performed without ACC and objective refraction (imaging 1) and with them (imaging 2). RESULTS: The interclass correlation coefficient (ICC) reflected high agreement between imaging 1 and imaging 2 in both groups. The ICC in the glaucoma and healthy groups for pRNFL (0.99 vs. 0.98), BMO (0.95 vs. 0.97), and MRW (1.0 vs. 1.0) was comparable. CONCLUSIONS: Our preliminary data from a small number of eyes showed that the measurements of pRNFL, MRW, and BMO reflected high agreement between both imaging techniques with ACC and objective refraction and without these parameters in subjects with a refractive error up to ± 6.0 diopters. Further studies with participants with higher refractive error are necessary to evaluate the impact of biometric parameters such as SE and ACC on measurements with SD-OCT.

SARS-CoV-2 in first trimester pregnancy: a cohort study.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

A distinctive epigenetic ageing profile in human granulosa cells.

STUDY QUESTION: Does women's age affect the DNA methylation (DNAm) profile differently in mural granulosa cells (MGCs) from other somatic cells? SUMMARY ANSWER: Accumulation of epimutations by age and a higher number of age-related differentially methylated regions (DMR) in MGCs were found compared to leukocytes from the same woman, suggesting that the MGCs have a distinctive epigenetic profile. WHAT IS KNOWN ALREADY: The mechanisms underlying the decline in women's fertility from the mid-30s remain to be fully elucidated. The DNAm age of many healthy tissues changes predictably with and follows chronological age, but DNAm age in some reproductive tissues has been shown to depart from chronological age (older: endometrium; younger: cumulus cells, spermatozoa). STUDY DESIGN, SIZE, DURATION: This study is a multicenter cohort study based on retrospective analysis of prospectively collected data and material derived from healthy women undergoing IVF or ICSI treatment following ovarian stimulation with antagonist protocol. One hundred and nineteen women were included from September 2016 to June 2018 from four clinics in Denmark and Sweden. PARTICIPANTS/MATERIALS, SETTING, METHODS: Blood samples were obtained from 118 healthy women with varying ovarian reserve status. MGCs were collected from 63 of the 119 women by isolation from pooled follicles immediately after oocyte retrieval. DNA from leukocytes and MGCs was extracted and analysed with a genome-wide methylation array. Data from the methylation array were processed using the ENmix package. Subsequently, DNAm age was calculated using established and tailored age predictors and DMRs were analysed with the DMRcate package. MAIN RESULTS AND ROLE OF CHANCE: Using established age predictors, DNAm age in MGCs was found to be considerable younger and constant (average: 2.7 years) compared to chronological age (average: 33.9 years). A Granulosa Cell clock able to predict the age of both MGCs (average: 32.4 years) and leukocytes (average: 38.8 years) was successfully developed. MGCs differed from leukocytes in having a higher number of epimutations (P = 0.003) but predicted telomere lengths unaffected by age (Pearson's correlation coefficient = -0.1, P = 0.47). DMRs associated with age (age-DMRs) were identified in MGCs (n = 335) and in leukocytes (n = 1) with a significant enrichment in MGCs for genes involved in RNA processing (45 genes, P = 3.96 × 10-08) and gene expression (152 genes, P = 2.3 × 10-06). The top age-DMRs included the metastable epiallele VTRNA2-1, the DNAm regulator ZFP57 and the anti-Müllerian hormone (AMH) gene. The apparent discordance between different epigenetic measures of age in MGCs suggests that they reflect difference stages in the MGC life cycle. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: No gene expression data were available to associate with the epigenetic findings. The MGCs are collected during ovarian stimulation, which may influence DNAm; however, no correlation between FSH dose and number of epimutations was found. WIDER IMPLICATIONS OF THE FINDINGS: Our findings underline that the somatic compartment of the follicle follows a different methylation trajectory with age than other somatic cells. The higher number of epimutations and age-DMRs in MGCs suggest that their function is affected by age. STUDY FUNDING/COMPETING INTEREST(S): This project is part of ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS, the Danish National Research Foundation and the European Research Council. The authors declare no conflict of interest.

Fast Peroxy Radical Isomerization and OH Recycling in the Reaction of OH Radicals with Dimethyl Sulfide.

Dimethyl sulfide (DMS), produced by marine organisms, represents the most abundant, biogenic sulfur emission into the Earth's atmosphere. The gas-phase degradation of DMS is mainly initiated by the reaction with the OH radical forming first CH3SCH2O2 radicals from the dominant H-abstraction channel. It is experimentally shown that these peroxy radicals undergo a two-step isomerization process finally forming a product consistent with the formula HOOCH2SCHO. The isomerization process is accompanied by OH recycling. The rate-limiting first isomerization step, CH3SCH2O2 → CH2SCH2OOH, followed by O2 addition, proceeds with k = (0.23 ± 0.12) s-1 at 295 ± 2 K. Competing bimolecular CH3SCH2O2 reactions with NO, HO2, or RO2 radicals are less important for trace-gas conditions over the oceans. Results of atmospheric chemistry simulations demonstrate the predominance (≥95%) of CH3SCH2O2 isomerization. The rapid peroxy radical isomerization, not yet considered in models, substantially changes the understanding of DMS's degradation processes in the atmosphere.

[Recommendations for the perioperative use of dipyrone : Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association]. / Empfehlungen zur perioperativen Anwendung von Metamizol : Expertenempfehlung des Arbeitskreises Akutschmerz der Deutschen Schmerzgesellschaft, des Wissenschaftlichen Arbeitskreises Schmerzmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin und der Chirurgischen Arbeitsgemeinschaft Akutschmerz der Deutschen Gesellschaft für Chirurgie unter Beteiligung von Vertretern der Arzneimittelkommission der deutschen Ärzteschaft.

BACKGROUND: Dipyrone (metamizole) is widely used for perioperative pain management in countries where it is marketed; however, uncertainty exists concerning the safe use of this drug, specifically considering the rare adverse event of an agranulocytosis. METHODS: As evidence from published studies was lacking, an expert panel developed recommendations for the perioperative use of dipyrone. After a formal, structured consensus process, the recommendations were approved by the involved medical societies. RESULTS: The panel agreed that blood cell counts shall not be standard for short-term perioperative use in patients unless they are at risk for neutropenia. The medical staff shall be aware of the symptoms and course of action when agranulocytosis is suspected. Patients shall be informed about the risks and benefits of dipyrone and about potential alternatives. The expert group concluded that dipyrone has a relatively positive risk-benefit ratio compared to other nonopioid analgesics. The group strongly recommended educating patients about the symptoms of agranulocytosis if they have received dipyrone over several days and/or treatment is to be continued after discharge, because agranulocytosis can occur several days after discontinuation of metamizole. Further recommendations refer to the information of the physician taking over the patient's care after discharge and the avoidance of re-exposure in patients having previously suffered from dipyrone-induced agranulocytosis. CONCLUSION: The group's recommendations shall be communicated in order to raise medical staff's and patients' awareness of the appropriate use of dipyrone in the perioperative period.

[Recommendations for the perioperative use of dipyrone : Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association]. / Empfehlungen zur perioperativen Anwendung von Metamizol : Expertenempfehlung des Arbeitskreises Akutschmerz der Deutschen Schmerzgesellschaft, des Wissenschaftlichen Arbeitskreises Schmerzmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin und der Chirurgischen Arbeitsgemeinschaft Akutschmerz der Deutschen Gesellschaft für Chirurgie unter Beteiligung von Vertretern der Arzneimittelkommission der deutschen Ärzteschaft.

BACKGROUND: Dipyrone (metamizole) is widely used for perioperative pain management in countries where it is marketed; however, uncertainty exists concerning the safe use of this drug, specifically considering the rare adverse event of an agranulocytosis. METHODS: As evidence from published studies was lacking, an expert panel developed recommendations for the perioperative use of dipyrone. After a formal, structured consensus process, the recommendations were approved by the involved medical societies. RESULTS: The panel agreed that blood cell counts shall not be standard for short-term perioperative use in patients unless they are at risk for neutropenia. The medical staff shall be aware of the symptoms and course of action when agranulocytosis is suspected. Patients shall be informed about the risks and benefits of dipyrone and about potential alternatives. The expert group concluded that dipyrone has a relatively positive risk-benefit ratio compared to other nonopioid analgesics. The group strongly recommended educating patients about the symptoms of agranulocytosis if they have received dipyrone over several days and/or treatment is to be continued after discharge, because agranulocytosis can occur several days after discontinuation of metamizole. Further recommendations refer to the information of the physician taking over the patient's care after discharge and the avoidance of re-exposure in patients having previously suffered from dipyrone-induced agranulocytosis. CONCLUSION: The group's recommendations shall be communicated in order to raise medical staff's and patients' awareness of the appropriate use of dipyrone in the perioperative period.

[Recommendations for the perioperative use of dipyrone : Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association]. / Empfehlungen zur perioperativen Anwendung von Metamizol : Expertenempfehlung des Arbeitskreises Akutschmerz der Deutschen Schmerzgesellschaft, des Wissenschaftlichen Arbeitskreises Schmerzmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin und der Chirurgischen Arbeitsgemeinschaft Akutschmerz der Deutschen Gesellschaft für Chirurgie unter Beteiligung von Vertretern der Arzneimittelkommission der deutschen Ärzteschaft.

BACKGROUND: Dipyrone (metamizole) is widely used for perioperative pain management in countries where it is marketed; however, uncertainty exists concerning the safe use of this drug, specifically considering the rare adverse event of an agranulocytosis. METHODS: As evidence from published studies was lacking, an expert panel developed recommendations for the perioperative use of dipyrone. After a formal, structured consensus process, the recommendations were approved by the involved medical societies. RESULTS: The panel agreed that blood cell counts shall not be standard for short-term perioperative use in patients unless they are at risk for neutropenia. The medical staff shall be aware of the symptoms and course of action when agranulocytosis is suspected. Patients shall be informed about the risks and benefits of dipyrone and about potential alternatives. The expert group concluded that dipyrone has a relatively positive risk-benefit ratio compared to other nonopioid analgesics. The group strongly recommended educating patients about the symptoms of agranulocytosis if they have received dipyrone over several days and/or treatment is to be continued after discharge, because agranulocytosis can occur several days after discontinuation of metamizole. Further recommendations refer to the information of the physician taking over the patient's care after discharge and the avoidance of re-exposure in patients having previously suffered from dipyrone-induced agranulocytosis. CONCLUSION: The group's recommendations shall be communicated in order to raise medical staff's and patients' awareness of the appropriate use of dipyrone in the perioperative period.

[Combined XEN and Baerveldt implant-principles and management of complications]. / Kombiniertes XEN-Baerveldt-Implantat ­ Prinzip und Management von Komplikationen.

The treatment of congenital glaucoma requires special expertise and often novel surgical approaches. The combined use of a XEN and a Baerveldt implant is an alternative to conventional tube implants and may be less harmful for long-term corneal endothelial damage. If this technique does not provide sufficient long-term control of intraorbital pressure (IOP), a direct implantation of the Baerveldt tube can be easily performed in a second intervention.

[Management of anticoagulants in ophthalmic surgery-a survey among ophthalmic surgeons in Germany]. / Umgang mit gerinnungshemmenden Substanzen in der Ophthalmochirurgie ­ eine Umfrage unter Ophthalmochirurgen in Deutschland.

INTRODUCTION: As our population ages and comorbidities rise, ophthalmic surgeons are increasingly faced with patients on anticoagulant therapy or with clotting disorders. The ophthalmic surgeon has to weigh the perioperative risk of haemorrhage when anticoagulation continues against the risk of thromboembolism caused by discontinuation or changing the patient's medication (bridging, switching, cessation). There are currently no guidelines or recommendations. METHODS: A survey was sent to the DOG (German Ophthalmologic Society) divisions and associated surgical organizations to determine the status quo. A questionnaire was sent out and filled out by the different groups of specialists. RESULTS: All four divisions of the DOG and four associated organizations returned completed questionnaires. Surgical interventions were listed that are carried out during anticoagulant therapy without exceptions, as well as interventions that were classified to require medical adjustment. Although the assessments varied, general consensus was achieved regarding interventions not requiring adjustments due to anticoagulants (i. e., intravitreal injection, cataract surgery, laser and corneal operations, simple muscle surgery), and those interventions requiring adjustments in medications (glaucoma operations, complex retina surgery, eye socket surgery, complex surgery of the lid). CONCLUSION: Main result of this survey was the specification of serious bleeding complications which are permanent vision loss and re-operation. They could serve as endpoint parameters for essential future investigations. Nevertheless, this survey makes clear that the decision about an adjustment of anticoagulant medication in ophthalmic surgery is currently made individually and not based on established standards.

[Trabeculectomy with mitomycin C : Video article]. / Trabekulektomie mit Mitomycin C : Videobeitrag.

Trabeculectomy is the most proven method for the treatment of open angle glaucoma. The long-term results of this method show an 80% success rate in lowering intraocular pressure over 20 years. The surgical technique is demonstrated in detail with the help of a video of the operation and which is available online. For more than 15 years trabeculectomy has been performed with the use of antifibrotic substances, such as mitomycin C. Long-term treatment with antiglaucoma eyedrops leads to a proven inflammation of the conjunctiva and the ocular surface with an increase in lymphocytes, mast cells, and fibroblasts. Discontinuation of antiglaucoma therapy in turn allows regeneration of the ocular surface. From the knowledge gained from these histopathological studies it has been recommended to stop glaucoma treatment prior to glaucoma surgery and to pretreat the conjunctiva with eyedrops containing cortisone. Administration of nonsteroidal antiphlogistic substances or local steroids to the conjunctiva 4 weeks prior to surgery increases long-term success of the filtering bleb function.

Predictors of Atrial Fibrillation Recurrence after Catheter Ablation: Data from the German Ablation Registry.

Catheter ablation (CA) for atrial fibrillation (AF) has emerged as a widespread first or second line treatment option. However, up to 45% of patients (pts) show recurrence of AF within 12 month after CA. We present prospective multicenter registry data comparing characteristics of pts with and without recurrence of AF within the first year after CA. This study comprises all pts with complete follow-up one year after CA (1-y-FU; n = 3679). During 1y-FU in 1687 (45.9%) pts recurrence of AF occurred. The multivariate analysis revealed female sex and AF type prior to the procedure as predictors for AF recurrence. Furthermore, comorbidities such as valvular heart disease and renal failure as well as an early AF relapse were also predictors of AF recurrence during 1-y-FU. However, despite an AF recurrence rate of 45.9%, the majority of these pts (72.4%) reported a significant alleviation of clinical symptoms. In conclusion in pts with initially successful CA for AF female sex, AF type, in-hospital AF relapse and comorbidities such as renal failure and valvular heart disease are independent predictors for AF recurrence during 1-y-FU. However, the majority of pts deemed their interventions as successful with significant reduction of symptoms irrespective of AF.

[Professional skills and advanced training for residents in ophthalmology]. / Qualifikation und Weiterbildung in der Facharztausbildung.

Career paths have become very complex and variable in the field of ophthalmology. The common way of ophthalmologists in private practice is still a very popular model, especially with regard to the autonomy which has been missing for years in hospitals. It is still an attractive way but alternative developmental options which appear more exciting and flexible, are on the increase.

Long-range transport of Xe-133 emissions under convective and non-convective conditions.

To investigate the transport of xenon emissions, the Provisional Technical Secretariat (PTS) operates an Atmospheric Transport Modelling (ATM) system based on the Lagrangian Particle Dispersion Model FLEXPART. The air mass trajectory ideally provides a "link" between a radionuclide release and a detection confirmed by radionuclide measurements. This paper investigates the long-range transport of Xe-133 emissions under convective and non-convective conditions, with special emphasis on evaluating the changes in the simulated activity concentration values due to the inclusion of the convective transport in the ATM simulations. For that purpose a series of 14 day forward simulations, with and without convective transport, released daily in the period from 1 January 2011 to 30 June 2013, were analysed. The release point was at the ANSTO facility in Australia. The simulated activity concentrations for the period January 2011 to February 2012 were calculated using the daily emission values provided by the ANSTO facility; outside the aforementioned period, the median daily emission value was used. In the simulations the analysed meteorological input data provided by the European Centre for Medium-Range Weather Forecasts (ECMWF) were used with the spatial resolution of 0.5°. It was found that the long-range transport of Xe-133 emissions under convective conditions, where convection was included in the ATM simulation, led to a small decrease in the activity concentration, as compared to transport without convection. In special cases related to deep convection, the opposite effect was observed. Availability of both daily emission values and measured Xe-133 activity concentration values was an opportunity to validate the simulations. Based on the paired t-test, a 95% confidence interval for the true mean difference between simulations without convective transport and measurements was constructed. It was estimated that the overall uncertainty lies between 0.08 and 0.25 mBq/m3. The uncertainty for the simulations with the convective transport included is slighted shifted to the lower values and is in the range between 0.06 and 0.20 mBq/m3.

Revision of encapsulated blebs after trabeculectomy: Long-term comparison of standard bleb needling and modified needling procedure combined with transconjunctival scleral flap sutures.

PURPOSE: To compare two surgical approaches for treating encapsulated blebs after trabeculectomy with mitomycin C, in terms of the development of intraocular pressure and progression of glaucoma in a long-term follow up: 1. bleb needling alone vs. 2. a combined approach of needling with additional transconjunctival scleral flap sutures, to prevent early ocular hypotony. METHODS: Forty-six patients with failing blebs after trabeculectomy with mitomycin C were enrolled in this study. Patients received either needling revision alone (group 1; n = 23) or a combined needling with additional transconjuctival flap sutures, if intraoperatively the intraocular pressure was estimated to be low (group 2; n = 23). Intraocular pressure (IOP), visual acuity, visual fields, and optic nerve head configuration by means of Heidelberg Retina Tomograph (HRT®) were analysed over time. Results from both groups were compared using Mann-Whitney U-test for single timepoints. RESULTS: IOP did not differ significantly between the two groups during follow-up at three months (P = 0.13), six months (P = 0.12), one year (P = 0.92) and two years (P = 0.57) after surgery. Furthermore, there was no significant difference in the course of glaucoma concerning the optic nerve anatomy between the two groups (Rim Area Change in the Moorfields Regression Analysis of HRT®) till two years after surgery (P = 0.289). No functional impairment in visual acuity and visual fields was found in the groups of the study. CONCLUSIONS: Single needling procedure is a standard successful method for restoring the function of encapsulated blebs. Postoperative hypotony represents a possible hazard, which can be minimized by additional transconjunctival flap sutures. Long-term results suggest that this modification is equally effective in lowering the IOP and preventing the progression of glaucoma as the standard needling procedure. To our knowledge this is the first study to investigate the long-term effect of tranconjunctival sutures for the prevention of hypotony.

Prevalence of hearing loss in Northern and Southern Germany.

BACKGROUND: The HÖRSTAT study conducted in Northwest Germany found hearing impairment in approximately 16% of adults when applying the World Health Organization (WHO) criterion. However, the robustness of extrapolations to a national level might be questioned, as the epidemiological data were collected on a regional level. METHODS: Independently from HÖRSTAT, the "Hearing in Germany" study examined adult hearing in Aalen, a town located in Southwest Germany. Both cross-sectional studies were based on stratified random samples from the general population. The average pure-tone threshold shift at 0.5, 1, 2, and 4 kHz (PTA4), the prevalence of hearing impairment (WHO criterion: PTA4 in the better ear >25), and hearing aid uptake were compared. Data from the Aalen and HÖRSTAT studies were pooled (n = 3105) to extrapolate to the prevalence and the degree of hearing impairment for the years 2015, 2020, and 2025. RESULTS: Both studies yielded very similar results for PTA4. Weighted for official population statistics, the prevalence of hearing impairment according to the WHO criterion is 16.2% in adults, thus affecting 11.1 million persons in Germany. Owing to demographic changes, the prevalence is expected to increase in the medium term by around 1% per 5­year period. With a similar degree of hearing loss, hearing aid provision differs from place to place. CONCLUSION: When adjusted for gender and age to the European Standard Population, the prevalence of hearing impairment observed both in HÖRSTAT and the Aalen sample is considerably lower than reported for international studies. Since the analysis refers to cross-sectional data only, possible cohort effects are not considered in the prevalence projection.

[Prevalence of hearing loss in Northern and Southern Germany. German version]. / Prävalenz von Schwerhörigkeit in Nord- und Süddeutschland.

BACKGROUND: The HÖRSTAT study conducted in Northwest Germany yielded hearing impairment in approximately 16% of adults according to the World Health Organization (WHO) criterion. However, the robustness of extrapolations on a national level might be questioned, as the epidemiological data were collected on a regional level. METHODS: Independently from HÖRSTAT, the "Hearing in Germany" study examined adult hearing in Aalen, a town located in Southwest Germany. Both cross-sectional studies were based on stratified random samples from the general population. Pure-tone average at 0.5, 1, 2, and 4 kHz (PTA4), the prevalence of hearing impairment (WHO criterion: PTA4 in the better ear >25 dB HL), and hearing aid provision were compared. Data from the Aalen study and HÖRSTAT were pooled (n = 3105) to extrapolate the prevalence and degree of hearing impairment for the years 2015, 2020, and 2025. RESULTS: Both studies show very similar results for PTA4. Weighted for official population statistics, the prevalence of hearing impairment according to the WHO criterion is 16.2% among adults, affecting 11.1 million persons in Germany. Due to demographic changes, the prevalence is expected to increase in the medium term by around 1% per 5­year period. With a similar degree of hearing loss, hearing aid provision differs from place to place. CONCLUSION: Adjusted for gender and age to the European Standard Population (ESP), the prevalence of hearing impairment observed both in HÖRSTAT and the Aalen sample is considerably lower than reported for international studies. Since the analysis refers to cross-sectional data only, possible cohort effects are not considered in the prevalence projection.

Disseminated histoplasmosis and AIDS: a prospective and multicentre study to evaluate the performance of different diagnostic tests.

The burden of histoplasmosis has been poorly documented in most of the endemic areas for the disease, including Brazil. Also, modern non-culture-based diagnostic tests are often non-available in these regions. This was a prospective cohort study in HIV-infected patients with suspected disseminated disease evaluated with different diagnostic tests. Patients were enrolled in three referral medical centres in Porto Alegre, Brazil. Among 78 evaluated patients, disseminated histoplasmosis was confirmed in eight individuals (10.3%) by the means of classical (culture/histopathology) tests. Antigen detection in the urine was found to be more sensitive: IMMY® ALPHA ELISA detected 13 positive cases (16.7%) and the in-house ELISA test developed by the Centers for Disease Prevention and Control (CDC) detected 14 (17.9%). IMMY® and CDC tests provided concordant results in 96.2% of cases. This is the first study to compare the performance of the in-house CDC ELISA test with the IMMY® commercial test for the diagnosis of histoplasmosis, and a high degree of concordance was observed. The study revealed that H. capsulatum is an important agent of disseminated disease in AIDS patients in Brazil, reinforcing the importance of making available modern diagnostic tests as well as safer antifungal agents for the treatment of histoplasmosis.