Next generation sequencing in adult patients with glioblastoma in Switzerland: a multi-centre decision analysis.

BACKGROUND: Glioblastoma is the most common malignant primary brain tumour in adults and driven by various genomic alterations. Next generation sequencing (NGS) provides timely information about the genetic landscape of tumours and might detect targetable mutations. To date, differences exist in the application and NGS assays used as it remains unclear to what extent these variants may affect clinical decision making. In this survey-based study, we investigated the use of NGS in adult patients with glioblastoma in Switzerland. METHODS: All eight primary care centres for Neuro-Oncology in Switzerland participated in this survey. The NGS assays used as well as the criteria for the application of NGS in newly diagnosed glioblastoma were investigated. Decision trees were analysed for consensus and discrepancies using the objective consensus methodology. RESULTS: Seven out of eight centres perform NGS in patients with newly diagnosed glioblastoma using custom made or commercially available assays. The criteria most relevant to decision making were age, suitability of standard treatment and fitness. NGS is most often used in fitter patients under the age of 60 years who are not suitable for standard therapy, while it is rarely performed in patients in poor general health. CONCLUSION: NGS is frequently applied in glioblastomas in adults in Neuro-Oncology centres in Switzerland despite seldom changing the course of treatment to date.

Using Satellite Observations to Evaluate Model Microphysical Representation of Arctic Mixed-Phase Clouds.

Mixed-phase clouds play an important role in determining Arctic warming, but are parametrized in models and difficult to constrain with observations. We use two satellite-derived cloud phase metrics to investigate the vertical structure of Arctic clouds in two global climate models that use the Community Atmosphere Model version 6 (CAM6) atmospheric component. We report a model error limiting ice nucleation, produce a set of Arctic-constrained model runs by adjusting model microphysical variables to match the cloud phase metrics, and evaluate cloud feedbacks for all simulations. Models in this small ensemble uniformly overestimate total cloud fraction in the summer, but have variable representation of cloud fraction and phase in the winter and spring. By relating modeled cloud phase metrics and changes in low-level liquid cloud amount under warming to longwave cloud feedback, we show that mixed-phase processes mediate the Arctic climate by modifying how wintertime and springtime clouds respond to warming.

Early gamma-oscillations as correlate of localized nociceptive processing in primary sensorimotor cortex.

Recent studies put forward the idea that stimulus-evoked gamma-band oscillations (GBOs; 30-100 Hz) play a specific role in nociception. So far, evidence for the specificity of GBOs for nociception, their possible involvement in nociceptive sensory discriminatory abilities, and knowledge regarding their cortical sources is just starting to grow. To address these questions, we used electroencephalography (EEG) to record brain activity evoked by phasic nociceptive laser stimuli and tactile stimuli applied at different intensities to the right hand and foot of 12 healthy volunteers. The EEG was analyzed in the time domain to extract phase-locked event-related brain potentials (ERPs) and in three regions of interest in the time-frequency domain (delta/theta, 40-Hz gamma, 70-Hz gamma) to extract stimulus-evoked changes in the magnitude of non-phase-locked brain oscillations. Both nociceptive and tactile stimuli, matched with respect to subjective intensity, elicited phase locked ERPs of increasing amplitude with increasing stimulus intensity. In contrast, only nociceptive stimuli elicited a significant enhancement of GBOs (65-85 Hz, 150-230 ms after stimulus onset), whose magnitude encoded stimulus intensity, whereas tactile stimuli led to a GBO decrease. Following nociceptive hand stimulation, the topographical distribution of GBOs was maximal at contralateral electrode C3, whereas maximum activity following foot stimulation was recorded at the midline electrode Cz, compatible with generation of GBOs in the representations of the hand and foot of the primary sensorimotor cortex, respectively. The differential behavior of high-frequency GBOs and low-frequency 40-Hz GBOs is indicating different functional roles and regions in sensory processing.NEW & NOTEWORTHY Gamma-band oscillations show hand-foot somatotopy compatible with generation in primary sensorimotor cortex and are present following nociceptive but not tactile stimulation of the hand and foot in humans.

The Transatlantic HbA1c gap: differences in glycaemic control across the lifespan between people included in the US T1D Exchange Registry and those included in the German/Austrian DPV registry.

AIM: To compare HbA1c levels across the lifespan in people with type 1 diabetes in the USA with those in Germany/Austria, and to examine potential differences in HbA1c levels between sexes, insulin delivery methods and minority status. METHODS: Data were extracted from the US T1D Exchange Registry (n=18 381 participants from 73 sites) and from the German/Austrian Prospective Diabetes Follow-up Registry, the DPV (n=32 643 participants from 362 sites). Mean HbA1c was calculated for each year of age for individuals aged ≤25 years, and at 2-year age intervals for individuals aged >25 years. Curves for mean HbA1c by age were estimated using locally weighted scatterplot smoothing. HbA1c differences between registries, sexes, insulin delivery methods, and minority status were assessed by age group using multiple linear regression. RESULTS: In both registries, mean HbA1c increased by ~11 mmol/mol (1.0%) between the ages of 9 and 18 years, although at quite different absolute levels: from 66 mmol/mol (8.2%) to 77 mmol/mol (9.2%) in the T1D Exchange Registry, and from 56 mmol/mol (7.3%) to 66 mmol/mol (8.2%) in the DPV. Sex differences were observed in the DPV only. In the T1D Exchange Registry, injection users had higher mean HbA1c than pump users across the lifespan, whereas in the DPV higher HbA1c levels in injection users were observed in the age groups 6 to <12 years, 12 to <18 years, and 30 to <50 years (P < 0.001). Minority status was significantly associated with higher HbA1c in most age groups in both registries. CONCLUSIONS: Significant differences in HbA1c were noted between the USA and Germany/Austria, with disparities more pronounced in early childhood through to young adulthood. Further studies should identify causes for these disparities.

Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study.

Background: The vascular endothelial growth factor antibody bevacizumab (Avastin®), received approval for the treatment of recurrent glioblastoma in many countries including the USA and Switzerland, but not the European Union, in 2009. Here, we explored the hypothesis that the approval of bevacizumab improved outcome with glioblastoma on a population level. Patients and methods: The prognostic significance of epidemiological, molecular genetic, and clinical data including treatment for glioblastoma patients diagnosed from 2010 to 2014 in the Canton of Zurich, Switzerland, was retrospectively analyzed using log-rank test and Cox proportional hazards models. Data were compared with data for the years 2005-2009. Results: In total, 310 glioblastoma patients were identified in the years 2010-2014. Median overall survival was 13.5 months for patients with known isocitrate dehydrogenase (IDH) wild-type (wt) (IDH1R132H-non-mutant) tumors (N = 248), compared with 11.3 months for IDH wt patients (P = 0.761) before (2005-2009). In the IDH wt cohort, bevacizumab use at any time increased from 19% in 2005-2009 to 49% in 2010-2014. Multivariate analysis did not identify bevacizumab exposure at any time to be associated with survival. Yet, upon the second-line treatment, baseline doses of corticosteroids were reduced by more than half in 83% of patients on bevacizumab compared with 48% of the patients treated with bevacizumab-free regimens (P = 0.007). Conclusion: This epidemiological study of a small, but clinically well-annotated patient cohort fails to support the assumption that the strong increase of bevacizumab use since 2010 improved survival in glioblastoma although clinical benefit associated with decreased steroid use may have been achieved.

High proportion of patients with bleeding of unknown cause in persons with a mild-to-moderate bleeding tendency: Results from the Vienna Bleeding Biobank (VIBB).

INTRODUCTION: Data on clinical characteristics and the prevalence of underlying coagulopathies in patients with mild-to-moderate bleeding disorders (MBDs) are scarce. AIM: We established the Vienna Bleeding Biobank (VIBB) to characterize and thoroughly investigate Austrian patients with MBDs. RESULTS: Four hundred eighteen patients (female = 345, 82.5%) were included. A platelet function defect (PFD) was diagnosed in 26 (6.2%) and a possible PFD in 30 (7.2%) patients. Eight patients (1.9%) were diagnosed with von Willebrand disease (VWD) (type 1 n = 6; type 2 n = 2), and 29 patients had low VWF (30-50 IU/dL). Deficiencies in factor VIII, IX, XI or XIII were found in 11 (2.6%), 3 (0.7%), 3 (0.7%) and 1 patient(s), 2 patients had dysfibrinogenaemia, and further 2 had possible PFD and FXI deficiency. Probable causal mutations were detected in 8 of 11 patients with FVIII deficiency, 2 of 3 patients with FIX deficiency and 2 of 8 patients with VWD. Three hundred three patients (72.5%) had normal results in the coagulation assays and were categorized as patients with bleeding of unknown cause (BUC). The bleeding score did not differ between patients with and without established diagnosis. A diagnosis of a bleeding disorder was more frequently made in men than in women (49.3% vs 22.9%). Male sex (OR 3.55, 95% CI: 2.02-6.22; P < .001) and blood group 0 (OR 1.86, 95% CI: 1.17-2.94; P = .008) were independently associated with diagnosis of a bleeding disorder. CONCLUSION: The high rate of patients with BUC despite in-depth haemostatic assessment underlines the incompleteness of available routine laboratory tests. Males with MBDs were more likely to be diagnosed with an established bleeding disorder than females.

Risk factors for necrobiosis lipoidica in Type 1 diabetes mellitus.

AIMS: To compare the clinical and metabolic characteristics of patients with Type 1 diabetes and necrobiosis lipoidica with those of patients with Type 1 diabetes who do not have necrobiosis lipoidica. A multicentre analysis was performed. METHODS: Clinical and laboratory data were obtained from 64 133 patients (aged 0-25 years) with Type 1 diabetes with and without necrobiosis lipoidica who were registered in the German/Austrian Diabetes Prospective Documentation Initiative registry. Data were analysed using multivariable regression modelling. Age, diabetes duration, treatment year and sex were considered as confounding factors. RESULTS: Results adjusted for demographic variables are presented. In patients with necrobiosis lipoidica, metabolic control was worse (HbA1c 72 vs. 67 mmol/mol, 8.7% vs. 8.3%; P = 0.0065) and the duration of diabetes was longer [6.24 (3.28-9.97) vs. 5.11 (2.08-8.83) years; P = 0.014; not adjusted]. Patients with necrobiosis lipoidica required higher insulin doses than those without (1.02 vs. 0.92 U/kg/day; P < 0.0001). There was no significant difference in the frequency of microvascular complications (microalbuminuria and retinopathy) between the groups. Furthermore, 24.8% and 17.5% of patients with Type 1 diabetes with and without necrobiosis lipoidica, respectively, had elevated thyroid antibodies (P = 0.051). Necrobiosis lipoidica was correlated with coeliac disease in patients with Type 1 diabetes (3.4% vs. 1.0%; P = 0.0035). CONCLUSIONS: Our data indicate a strong correlation between hyperglycaemia and the development of necrobiosis lipoidica. We postulate that the underlying pathogenic processes differ from those leading to microalbuminuria and retinopathy, and additional immunological mechanisms may play a role.

[Management of hemorrhage in patients treated with direct oral anticoagulants]. / Management von Blutungen unter Therapie mit direkten oralen Antikoagulanzien.

The introduction of nonvitamin K antagonistic, direct oral anticoagulants (DOAC) made thromboembolic prophylaxis easier for patients. For many physicians, however, there is still uncertainty about monitoring, preoperative discontinuation, and restarting of DOAC therapy. Guidelines for the management of bleeding are provided, but require specific therapeutic skills in the management of diagnostics and therapy of acute hemorrhage. Small clinical studies and case reports indicate that unspecific therapy with prothrombin complex concentrates (PCC) and activated PCC (aPCC) concentrate may reverse DOAC-induced anticoagulation. However, PCC or aPCC at higher doses potentially provoke thromboembolic complications. However, idarucizumab, a specific, fast-acting, antidote for dabigatran, provides immediate and sustained reversal with no intrinsic or prohemostatic activity. This review article provides an overview of the pharmacology and potential risk of DOAC and the management in the perioperative period with a focus of current concepts in the treatment of DOAC-associated bleeding.

[Morel-Lavallée lesion : Severely injured 13 year old after being run over]. / Morel-Lavallée-Läsion : Schwerstverletzte 13-Jährige nach Überrolltrauma.

Accidents in which a person is run over are often associated with multiple serious injuries. Immediate bleeding control is crucial. Pressure and shear stress at the borders of subcutaneous tissue to the muscle fascia can cause hypoperfusion and the emergence of blood-filled cavities that are associated with a high risk of infection and necrosis, a so-called Morel-Lavallée lesion. Insufficient therapy can lead to local complications and furthermore to live-threatening sepsis.

Psychometric evaluation of the Sinhalese version of MacNew Heart Disease Health Related Quality of Life Questionnaire in patients with stable angina.

BACKGROUND: A Sinhalese version of a validated, disease-specific patient-reported heart disease health related quality of life instrument is lacking. The purpose of this study was to validate the interviewer-administered Sinhalese version of the MacNew Heart Disease Health-related Quality of Life Questionnaire (MacNew) in patients with clinically diagnosed stable angina. METHODS: The Sinhalese translation of the MacNew was carried using standard forward- backward translation technique. In this validation study, the MacNew was administered to 200 patients with stable angina. Reliability was assessed by internal consistency and test-retest reliability. Construct validity was explored by exploratory factor analysis using principal component analysis and confirmed by confirmatory factor analysis using the robust maximum likelihood method and known group comparison. The correlation between compatible domain scores of MacNew and the World Health Organization's quality of life -brief questionnaire was used to assess concurrent validity. RESULTS: The original 3-factor model (Physical, Emotional and Social) of the MacNew with cross-loadings was confirmed: principal component analysis with 53.42 % of the explained variance and confirmatory factor analysis with adequate fit for each of the three model fit criteria considered [root mean square error of approximation = 0.044 (90 % CI = 0.031 to 0.056); comparative fit index = 0.99; χ(2)/df = 1.39]. Internal consistency of the MacNew was acceptable with Cronbach's α of 0.92 on the Global scale and on the domain scales ranging from 0.85-0.91. Test-retest reliability was also found to be satisfactory with intraclass correlation coefficients of >0.9 for total and domain scores. A satisfactory level of concurrent validity was demonstrated with statistically significant correlations between compatible domain scores of MacNew and the World Health Organization's quality of life questionnaire (Pearson correlation ranging from 0.36-0.79). CONCLUSIONS: The interviewer-administered Sinhalese MacNew is a valid and reliable patient-reported outcome measure to assess disease specific health-related quality of life among Sinhalese patients with stable angina.

Bacterial and viral contamination of breathing circuits after extended use - an aspect of patient safety?

BACKGROUND: In the past, anaesthetic breathing circuits were identified as a source of pathogen transmission. It is still debated, whether breathing circuits combined with breathing system filters can be safely used for more than 1 day. The aim of this study was to evaluate the transmission risk of bacteria and also viruses via breathing circuits after extended use. METHODS: The inner and outer surface of 102 breathing circuits used for 1 day and of 101 circuits used for 7 days were examined for bacteria and viruses. Additionally, 10 and 20 breathing circuits each were examined after use on patients with pulmonary virus infection and with multidrug-resistant organism (MDRO) colonisation/infection respectively. Bacteria were detected by standard microbiological procedures; PCR techniques were applied for herpes simplex virus, cytomegalovirus, influenza, parainfluenza and respiratory syncytial virus. RESULTS: Endoluminal bacterial contamination of breathing circuits remained unchanged after 7-day vs. 1-day use (5.9% vs. 7.8%) [CI95%: -0.0886-0.0506, pnon-inferiority 0.0260]. Only outside surface contamination with bacteria belonging to environmental species or human flora increased (16.8 vs. 6.9%) [CI 95%: 0.0118 - 0.1876, pnon-inferiority 0.8660]. Viruses occurred on the patient side, but not in breathing circuits. No MDRO occurred in the 20 circuits after use on patients harbouring such germs. CONCLUSION: Endoluminal contamination of breathing circuits with bacteria did not increase after extended use. No viruses were detected in the breathing circuits using filters. Based on our results, the extended use of ABC without exceptions appears safe, if a high level of anaesthesia workplace cleaning is secured.

[Anesthesiological approach to postpartum hemorrhage]. / Anästhesiologisches Vorgehen bei peripartaler Blutung.

Peripartum hemorrhage (PPH) is a frequent obstetric emergency situation with increasing incidence in the last decades. It requires a fast, coordinated and interdisciplinary management. This life-threatening situation is often recognized too late and not adequately treated (too little is done too late); therefore, it is important to be aware of the most important risk factors for PPH known as the 4 Ts (i.e. tonus, trauma, tissue and thrombin). Due to the special patient population there is only little evidence-based data on hemostatic therapy in this situation; therefore, the currently available studies on the therapy of PPH is discussed.

[Human resource planning in operative anaesthesia : Structured interviews with 23 supervising senior physicians]. / Personaleinsatzplanung in der operativen Anästhesie : Strukturierte Interviews mit 23 personalverantwortlichen Oberärzten.

BACKGROUND: In the hospital, human resource planning has to consider the needs and preferences of personnel and planners as well as the financial interest of the hospital. Additionally, staff planning has become more complex due to a growing number of part-time doctors as well as a variety of working shifts. OBJECTIVES: The aim of the study was to describe existing human resource planning in German anesthesiology departments. Furthermore, we evaluated existing software solutions supporting human resource planning. MATERIALS AND METHODS: Anesthesiology departments of German university hospitals were enrolled in the study. The aspects covered were tools and time needed for planning, amount of conflicts while planning, components of the software solutions and the efficiency and satisfaction according to the users. This was evaluated for short-, intermediate- and long-term planning. Two groups were compared: departments with and without software exchanging information among the three planning periods. RESULTS: Out of 35 university anesthesiology departments, 23 took part in the survey. On average they employed 105.8 ± 27.8 doctors who had to cover 13.5 ± 6.3 different shifts during a weekday. Personnel planning is mostly done by senior physicians. In some departments, other staff, such as residents and junior doctors, were involved as well. Software that exchanged information between short-, intermediate- and long-term planning was used in 53 % of the departments (12 out of 23). Five departments used commercially available planning software: Polypoint Deutschland (PolypointDeutschland), Atoss (Atoss AG) and SP Expert (Interflex Datensysteme). The time needed for short-term planning was slightly reduced in the exchanging software group. No difference was shown for the intermediate planning period. The use of this software led to a slight reduction in planning conflicts and increased the self-estimated efficiency of the users (p = 0.02). Throughout all groups, the major complaint was missing interfaces, for example between the software and human resources department. The ideal planning software should reduce time needed for planning and prevent planning conflicts according to the interviewed physicians. Furthermore it should be flexible and transparent for all involved staff. CONCLUSIONS: This study analyzed structures established in human resource planning in the anesthesiology departments for the first time. Time for planning varies significantly in comparable departments indicating suboptimal processes. Throughout Germany, the requirements for human resources planning are similar; for example, the software should integrate all aspects of HR planning. Different approaches are under evaluation but so far no software solution has prevailed. The used solutions vary substantially and therefore a comparison is difficult. There is no software solution with wide adoption.

["Why mothers die". Learning from the analysis of anaesthesia-related maternal deaths (1985-2013)]. / "Why mothers die". Was wir von der Analyse anästhesiebedingter mütterlicher Sterbefälle (1985-2013) gelernt haben.

Every day, more than 800 women die from causes related to pregnancy or childbirth. Since 1952 the Confidential Enquiry of Maternal Deaths Reports (CEMD) have collected and analysed data on maternal mortality in the United Kingdom and Northern Ireland. This publication analyses the CEMD from 1985-2013 regarding anaesthesia- and analgesia related maternal deaths during pregnancy or peripartum. During this period, there has been a reduction in directly anaesthesia-related maternal deaths to 4.3%. Yet, an increase in anaesthesia-associated maternal deaths has been recorded. The rate of fatal complications during obstetric regional anaesthesia doubled in recent years, while the fatality risk for obstetric general anaesthesia has decreased. Many of the reported maternal deaths could presumably have been avoided. The anaesthesiologist has to be familiar with state-of-the-art, guideline-based concepts for anaesthesia during pregnancy, childbirth or post partum, especially using tools like simulation. Vital sign monitoring after obstetric anaesthesia has to be identical to other postoperative monitoring, and Modified Early Warning Scores should be used for this purpose. In regional anaesthesia, current standards for hygiene have to be adhered to and patients have to be visited after spinal/epidural anaesthesia. Interdisciplinary communication and collaboration still have to be improved; careful interdisciplinary planning of childbirth in high-risk obstetric patients is strongly advised.

[Complex control of the source of infection in sepsis : Extracorporeal membrane oxygenation (ECMO) as a bridging concept for tracheal fistula repair in sepsis-associated ARDS]. / Komplexe Fokussanierung in der Sepsis : Extrakorporale Membranoxygenierung (ECMO) als Bridging-Konzept zur trachealen Fistelsanierung bei sepsisassoziiertem ARDS.

Here, we present a case of a tracheal fistula due to an anastomotic insufficiency following abdominothoracic esophageal resection. Despite immediate discontinuity resection, the tracheal fistula could not be surgically closed, resulting in incomplete control of the source of infection and an alternative treatment concept in the form of interventional fistula closure using a Y-tracheal stent. However, owing to existing severe acute respiratory distress syndrome (ARDS), which is associated with a considerable risk of peri-interventional hypoxia, a temporary bridging concept using venovenous extracorporeal membrane oxygenation (ECMO) was implemented successfully.

Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2).

BACKGROUND: Gastro-oesophageal adenocarcinomas rarely metastasize to the central nervous system (CNS). The role of the human epidermal growth factor receptor 2 (HER2) in patients with these cancers and CNS involvement is presently unknown. PATIENTS AND METHODS: A multicentre registry was established to collect data from patients with gastro-oesophageal adenocarcinomas and CNS involvement both retrospectively and prospectively. Inclusion in the study required a predefined clinical data set, a central neuro-radiological or histopathological confirmation of metastatic CNS involvement and central assessment of HER2 by immunohistochemistry (IHC) and in situ hybridisation (ISH). In addition, expression of E-cadherin and DNA mismatch repair (MMR) proteins were assessed by IHC. RESULTS: One hundred patients fulfilled the inclusion criteria. The population's median age was 59 years (interquartile range: 54-68), of which 85 (85%) were male. Twenty-five patients were of Asian and 75 of Caucasian origin. HER2 status was positive in 36% (95% CI: 26.6-46.2) of cases. Median time from initial diagnosis to the development of brain metastases (BMets) or leptomeningeal carcinomatosis (LC) was 9.9 months (95% CI: 8.5-15.0). Median overall survival from diagnosis was 16.9 months (95% CI: 14.0-20.7) and was not related to the HER2 status. E-cadherin loss was observed in 9% of cases and loss of expression in at least one DNA MMR proteins in 6%. CONCLUSIONS: The proportion of a positive HER2 status in patients with gastro-oesophageal adenocarcinoma and CNS involvement was higher than expected. The impact of anti-HER2 therapies should be studied prospectively.

Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison.

AIMS: Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries. METHODS: Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex. RESULTS: Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15-24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available. CONCLUSION: These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.

Fertility preservation in cancer survivors.

Due to the increasing number of long-term cancer survivors, physicians of all specialties are confronted with the need to prevent side effects of the applied oncologic treatments. In the field of reproductive medicine fertility preservation has gained importance as most oncologic treatments have detrimental immediate or long-term impacts on male and female fertility. The American Society of Clinical Oncology and the American Society for Reproductive Medicine, as well as the recently founded International Society for Fertility Preservation propose several established and investigational options for fertility preservation. This review aims to summarize currently available techniques for fertility preservation and future perspectives in this field, as well as to provide recommendations for patient follow-up after cancer and during pregnancy.

[Metformin-induced lactic acidosis : Severe symptoms with difficult diagnostics]. / Metformininduzierte Laktatacidose : Schweres Krankheitsbild mit schwieriger Diagnosestellung.

Metformin-induced lactic acidosis is a rare but severe disease for the individual patients. A case of a 64-year-old patient with diabetes mellitus type 2 suffering from this disease is presented where metformin accumulation was caused by prerenal acute kidney failure. The clinical evaluation up to the final diagnosis, the pathophysiology and the appropriate therapy are presented in detail. Additionally, the current guidelines regarding the perioperative management of metformin administration are summarized. The case described aims to direct attention to the rare but, nevertheless, severe symptoms of metformin-induced lactic acidosis.

[Patient safety in anesthesiology : Multimodal strategies for perioperative care]. / Patientensicherheit in der Anästhesie : Multimodale Strategien für die perioperative Versorgung.

The concept of patient safety is more of a presence in modern day medicine than ever before. All measures and processes aiming at preempting and preventing critical incidents and accidents in patient care are collectively grouped under this concept. With the Declaration of Helsinki in 2010 modern anesthesiology has undertaken a fundamental role in the clinical implementation and perioperative clinicians are confronted with a multitude of theories, models, methods and tools targeted at improving or facilitating optimized patient safety. One of the biggest challenges lies in their synergistic combination to create a functioning concept for perioperative risk management while also incorporating individual strengths and weaknesses. The aim of the present paper is to provide a structured overview of the various components presently available for increasing perioperative patient safety.