Expertise in surgical neuro-oncology. Results of a survey by the EANS neuro-oncology section.

Introduction: Technical advances and the increasing role of interdisciplinary decision-making may warrant formal definitions of expertise in surgical neuro-oncology. Research question: The EANS Neuro-oncology Section felt that a survey detailing the European neurosurgical perspective on the concept of expertise in surgical neuro-oncology might be helpful. Material and methods: The EANS Neuro-oncology Section panel developed an online survey asking questions regarding criteria for expertise in neuro-oncological surgery and sent it to all individual EANS members. Results: Our questionnaire was completed by 251 respondents (consultants: 80.1%) from 42 countries. 67.7% would accept a lifetime caseload of >200 cases and 86.7% an annual caseload of >50 as evidence of neuro-oncological surgical expertise. A majority felt that surgeons who do not treat children (56.2%), do not have experience with spinal fusion (78.1%) or peripheral nerve tumors (71.7%) may still be considered experts. Majorities believed that expertise requires the use of skull-base approaches (85.8%), intraoperative monitoring (83.4%), awake craniotomies (77.3%), and neuro-endoscopy (75.5%) as well as continuing education of at least 1/year (100.0%), a research background (80.0%) and teaching activities (78.7%), and formal interdisciplinary collaborations (e.g., tumor board: 93.0%). Academic vs. non-academic affiliation, career position, years of neurosurgical experience, country of practice, and primary clinical interest had a minor influence on the respondents' opinions. Discussion and conclusion: Opinions among neurosurgeons regarding the characteristics and features of expertise in neuro-oncology vary surprisingly little. Large majorities favoring certain thresholds and qualitative criteria suggest a consensus definition might be possible.

[Prehospital postcardiac-arrest-sedation and -care in the Federal Republic of Germany-a web-based survey of emergency physicians]. / Präklinische Post-Cardiac-Arrest-Sedierung und -Behandlung in der Bundesrepublik Deutschland ­ eine webbasierte Umfrage unter notärztlichem Personal.

BACKGROUND: This study evaluates the implementation of postcardiac-arrest-sedation (PCAS) and -care (PRC) by prehospital emergency physicians in Germany. MATERIALS AND METHODS: Analysis of a web-based survey from October to November 2022. Questions were asked about implementation, medications used, complications, motivation for implementing or not implementing PCAS, and measures and target parameters of PRC. RESULTS: A total of 500 emergency physicians participated in the survey. In all, 73.4% stated that they regularly performed PCAS (hypnotics: 84.7%; analgesics: 71.1%; relaxants: 29.7%). Indications were pressing against the respirator (88.3%), analgesia (74.1%), synchronization to respirator (59.5%), and change of airway device (52.6%). Reasons for not performing PCAS (26.6%) included unconscious patients (73.7%); concern about hypotension (31.6%), re-arrest (26.3%), and worsening neurological assessment (22.5%). Complications of PCAS were observed by 19.3% of participants (acute hypotension [74.6%]); (re-arrest [32.4%]). In addition to baseline monitoring, PRC included 12-lead-electrocardiogram (96.6%); capnography (91.6%); catecholamine therapy (77.6%); focused echocardiography (20.6%), lung ultrasound (12.0%) and abdominal ultrasound (5.6%); induction of hypothermia (13.6%) and blood gas analysis (7.4%). An etCO2 of 35-45 mm Hg was targeted by 40.6%, while 9.0% of participants targeted an SpO2 of 94-98% and 19.2% of participants targeted a systolic blood pressure of ≥ 100 mm Hg. CONCLUSIONS: Prehospital PRC in Germany is heterogeneous and deviations from its target parameters are frequent. PCAS is frequent and associated with relevant complications. The development of preclinical care algorithms for PCAS and PRC within preclinical care seems urgently needed.

Microbiological profile and infection potential of different cryopreserved skull flaps after decompressive hemicraniectomy. Is cryopreservation at - 80 ℃ better?

OBJECTIVE: Patterns of cryopreservation of explanted skull bone flaps have long been a matter of debate, in particular the appropriate temperature of storage. To the best of our knowledge no study to date has compared the microbiological profile and the infection potential of skull bone flaps cryostored at the same institution at disparate degrees for neurosurgical purposes. In the context of our clinical trial DRKS00023283, we performed a bacterial culture of explanted skull bone flaps, which were cryopreserved lege artis at a temperature of either - 23 °C or - 80 °C after a decompressive hemicraniectomy. In a further step, we contaminated the bone fragments in a s uspension with specific pathogens (S. aureus, S. epidermidis and C. acnes, Colony forming unit CFU 103/ml) over 24 h and conducted a second culture. RESULTS: A total of 17 cryopreserved skull flaps (8: - 23 °C; 9: - 80 °C) explanted during decompressive hemicraniectomies performed between 2019 and 2020 as well as 2 computer-aided-designed skulls (1 vancomycin-soaked) were analyzed. Median duration of cryopreservation was 10.5 months (2-17 months). No microorganisms were detected at the normal bacterial culture. After active contamination of our skull flaps, all samples showed similar bacterial growth of above-mentioned pathogens; thus, our study did not reveal an influence of the storage temperature upon infectious dynamic of the skulls.

Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy.

BACKGROUND: Loss-of-function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. OBJECTIVES: To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy. METHODS: FLG mutations were analysed in 1836 infants in the Scandinavian population-based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age. RESULTS: FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3 g m-2  h-1 ) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95-4·28; P < 0·001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69-10·68) vs. 8·24 (95% CI 7·97-8·15), P < 0·01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25-2·80; P = 0·002 and OR 2·44, 95% CI 1·51-3·95; P < 0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04-2·22; P = 0·028 and OR 1·74, 95% CI 1·17-2·57; P = 0·005). FLG mutations were associated with eczema and AD in infancy. CONCLUSIONS: FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months.

Age at diagnosis of Type 2 diabetes in Germany: a nationwide analysis based on claims data from 69 million people.

AIM: For many European countries, including Germany, no valid estimates are available on age at diagnosis of Type 2 diabetes. Thus, we aimed to estimate the age at diagnosis in Germany. METHODS: Age at diagnosis of Type 2 diabetes in Germany was estimated based on Type 2 diabetes prevalence and incidence and the age distribution of the German population. Age- and sex-specific incidence and prevalence in 2014/2015, based on claims data from statutory health insurance (n= 69 000 000, ~85% of the German population), and the age pyramid for Germany in 2015 were used for the calculation. Age at Type 2 diabetes diagnosis was stratified by sex. CIs were estimated using bootstrap methods. In addition, the age range in which 50% of the population received a diagnosis of Type 2 diabetes was calculated (the interquartile range). RESULTS: The mean ± sd age at Type 2 diabetes diagnosis in 2015 was 61.0 ± 13.4 years (95% CI 60.9-61.0) in men. Women were diagnosed ~2 years later than men (mean age 63.4 ± 14.9 years; 95% CI 63.4-63.5). The age range in which 50% of the population was diagnosed with diabetes was 53-72 years for men and 54-76 years for women. CONCLUSIONS: The sex differences are mainly attributable to a higher incidence of Type 2 diabetes in men than women during middle age and the higher absolute number of women in the older ages. The early age at diabetes diagnosis compared to average life expectancy means that the risk of diabetes-related complications is increased.

Projected number of people with diagnosed Type 2 diabetes in Germany in 2040.

AIMS: To project the number of people with Type 2 diabetes in Germany between 2015 and 2040. METHODS: Based on data from 65 million insurees of the German statutory health insurance, we projected the age-specific prevalence of diabetes using mathematical relations between prevalence, incidence rate and mortality. We compared several scenarios regarding temporal trends in the incidence and mortality rate. The projected age-specific prevalence was applied to the projected age structure of the German population between 2015 and 2040 to calculate the number of people with Type 2 diabetes. RESULTS: Application of current age-specific prevalence estimates to the projected age structure in 2040, although ignoring temporal trends in incidence and mortality, yielded an increase in the number of Type 2 diabetes cases from 6.9 million in 2015 to 8.3 million (+21%) in 2040. More realistic scenarios that account for decreasing mortality rates and different trends in the incidence rates project between 10.7 million (+54%) and 12.3 million (+77%) Type 2 diabetes cases in 2040. CONCLUSIONS: For the first time, we projected the number of future Type 2 diabetes cases for the whole adult population in Germany. The results indicate a relative increase in the number of Type 2 diabetes cases of between 54% and 77% from 2015 to 2040. Temporal trends in the incidence rate are the main drivers of this increase. Simply applying current age-specific prevalence to the future age structure probably underestimates the future number of Type 2 diabetes cases.

Excess mortality for people diagnosed with type 2 diabetes in 2012 - Estimates based on claims data from 70 million Germans.

BACKGROUND AND AIMS: The hazard ratio (HR) is a meaningful concept for comparing the mortality of people with and without type 2 diabetes (T2D). Nevertheless, there is only one German study estimating age-specific HRs. Thus, this study aimed to provide population-wide age-specific HRs for Germany using a novel method based on aggregated population data. METHODS AND RESULTS: We used an illness-death model and published data on T2D prevalence and incidence as well as mortality in the German general population to estimate age-specific HRs in the year 2012 for the population aged 65-90 years. For men, the overall HR was 2.3, which decreased from 2.8 between 65 and 69 years old to 1.6 between 85 and 90 years old. For women, the overall HR was 3.0, which decreased from 4.2 to 1.7 in the same age groups, respectively. CONCLUSION: In Germany, men and women in 2012 with T2D aged 65-90 years experienced a three-to four-fold higher mortality compared to people without T2D, which might indicate that the excess mortality could be higher than in countries with comparable health care systems. Female sex and younger age were associated with higher excess mortality.

Utility of HbA1c and fasting plasma glucose for screening of Type 2 diabetes: a meta-analysis of full ROC curves.

AIMS: There is still debate on the optimal threshold for population-based screening of diabetes (diagnosed by the oral glucose tolerance test) using tests like HbA1c or fasting plasma glucose. Meta-analyses provide meaningful input in such situations. The aim of this article is to perform a meta-analysis that includes the complete information reported in the individual studies of two existing systematic reviews. METHODS: We screened the individual studies from two systematic reviews and reconstructed the full four-fold tables for every reported threshold. Using a recently proposed meta-analysis model for the comparison of two diagnostic tests, we compared HbA1c with fasting plasma glucose, and estimated meta-analytic receiver operating characteristic curves for both tests using the 11.1 mmol/l threshold of the 2-h post-challenge glucose level (2 h-PG) as the gold standard. RESULTS: We included nine studies from two existing systematic reviews in our analysis. Based on our data set, the optimal threshold lies between 42 and 44 mmol/mol (6.0-6.2%) for HbA1c , and 6.2-6.4 mmol/l for fasting plasma glucose choosing the Youden index as the technical criterion. In addition, we found that there is no relevant difference in the performance of HbA1c and fasting plasma glucose. CONCLUSIONS: In our meta-analysis, we found that the optimal threshold with reference to the 2 h-PG should be chosen between 42 and 44 mmol/mol (6.0-6.2%) for HbA1c , and 6.2-6.4 mmol/l for fasting plasma glucose on the basis of maximal sensitivity and specificity.

Healthcare costs of Type 2 diabetes in Germany.

AIM: To describe for the first time the direct costs of Type 2 diabetes treatment by analysing nationwide routine data from statutory health insurance in Germany. METHODS: This cost-of-illness-study was based on a 6.8% random sample of all German people with statutory health insurance (4.3 out of 70 million people). The healthcare expenses show direct per capita costs from the payer perspective. Healthcare expenses for physicians, dentists, pharmacies, hospitals, sick benefits and other healthcare costs were considered. Per capita costs, cost ratios for people with Type 2 diabetes and without diabetes as well as diabetes-attributable costs were calculated. RESULTS: Per capita costs for people with Type 2 diabetes amounted to €4,957 in 2009 and €5,146 in 2010. People with Type 2 diabetes had 1.7-fold higher health expenses than people without diabetes. The largest differences in health expenses were found for prescribed medication from pharmacies (cost ratio diabetes/no diabetes: 2.2) and inpatient treatment (1.8). Ten percent of the total statutory health insurance expense, in total €16.1 billion, was attributable to the medical care of people with Type 2 diabetes. CONCLUSIONS: This nationwide study indicates that one in 10 Euros of healthcare expenses is spent on people with Type 2 diabetes in Germany. In the future, national statutory health insurance data can be used to quantify time trends of costs in the healthcare system.

Tuning the deposition of molecular graphene nanoribbons by surface functionalization.

We show that individual, isolated graphene nanoribbons, created with a molecular synthetic approach, can be assembled on functionalised wafer surfaces treated with silanes. The use of surface groups with different hydrophobicities allows tuning the density of the ribbons and assessing the products of the polymerisation process.

Meta-analysis of diagnostic tests accounting for disease prevalence: a new model using trivariate copulas.

In real life and somewhat contrary to biostatistical textbook knowledge, sensitivity and specificity (and not only predictive values) of diagnostic tests can vary with the underlying prevalence of disease. In meta-analysis of diagnostic studies, accounting for this fact naturally leads to a trivariate expansion of the traditional bivariate logistic regression model with random study effects. In this paper, a new model is proposed using trivariate copulas and beta-binomial marginal distributions for sensitivity, specificity, and prevalence as an expansion of the bivariate model. Two different copulas are used, the trivariate Gaussian copula and a trivariate vine copula based on the bivariate Plackett copula. This model has a closed-form likelihood, so standard software (e.g., SAS PROC NLMIXED) can be used. The results of a simulation study have shown that the copula models perform at least as good but frequently better than the standard model. The methods are illustrated by two examples.

Effective diameter of the aortic annulus prior to transcatheter aortic valve implantation: influence of area-based versus perimeter-based calculation.

In computed tomography (CT) evaluation prior to transcatheter aortic valve implantation area- and perimeter-based calculation of the aortic annulus diameter, the so-called effective annulus diameter (ED), is the preferred parameter for decision making regarding prosthesis sizes. Currently, it is unclear how relevant the differences between the two methods of measurement are and how they are influenced by the cardiac cycle. The aim of this study was to compare area- and perimeter-based measurements in computed tomography derived aortic annulus sizing. A total of 60 patients who underwent evaluation for transcatheter aortic valve implantation were included in this study. All patients received pre-procedural ECG gated CT. The aortic annulus area and perimeter were measured and the derived ED compared using parametric statistics and Bland and Altman analysis. The mean patient age was 80.2 ± 4 years. Systolic aortic annulus area and perimeter were higher compared to diastolic results (mean difference area 12.8 ± 24 mm(2) and perimeter 0.72 ± 1 mm; p = 0.009-0.068). Both the area- and perimeter-based ED had a good agreement within two standard deviations for systolic and diastolic measurements. Effective diameter measurements derived from the area were significantly smaller compared to perimeter-based measurements (mean difference: systolic 0.72 ± 0.3 mm and diastolic 0.81 ± 0.4 mm; p < 0.001). While the area-based ED was significantly influenced by the cardiac cycle with a mean difference of 0.4 ± 0.6 mm (p = 0.009), no significant difference was found for the perimeter-based ED (mean difference: 0.2 ± 0.4; p = 0.07). For patients undergoing CT evaluation prior to transcatheter aortic valve implantation, the perimeter-based effective annulus diameter provides a reliable parameter for annulus sizing without significant affection by the cardiac cycle and therefore facilitates annulus measurements with a single heart phase. However, perimeter-based diameters of the annulus are significantly larger than area-based diameters.

Cardioprotective effects of low-dose cyclosporin A added to histidine-tryptophan-ketoglutarate cardioplegia solution prior to total myocardial ischemia: an in vitro rabbit heart study.

BACKGROUND/AIMS: Mitochondrial permeability transition pore (MPTP) opening appears to play a key role in myocardial cell survival after ischemia-reperfusion injury and can be inhibited by cyclosporin A (CsA). We investigated whether low-dose CsA added to histidine-tryptophan-ketoglutarate (HTK) cardioplegia solution could improve myocardial protection during longer periods of global myocardial ischemia as encountered during cardiac surgery. METHODS: Rabbit hearts perfused on a Langendorff apparatus were arrested with cold HTK solution containing 1 µmol/l CsA. After 90 min of ischemia, the hearts were reperfused and pmax, max dp/dt, min dp/dt, myocardial stiffness, pO(2), coronary flow and heart rate recorded. Tissue ATP and malondialdehyde (MDA) were measured to assess cell energy content and oxidative stress, respectively. RESULTS: CsA-treated hearts recovered pmax (p = 0.026), max dp/dt (p = 0.028) and min dp/dt (p = 0.025) more quickly and to a greater extent than non-treated hearts. They required markedly less oxygen (p = 0.041) in the first 10 min of reperfusion. Hearts treated with CsA produced 44% less MDA (1.09 vs. 1.93, p = 0.008), while ATP levels were unchanged. CONCLUSIONS: HTK cardioplegia solution containing CsA at a dose well below that expected to cause systemic immunosuppressive effects leads to a significant and timelier recovery of myocardial contractility, while consuming less oxygen.

[Collagen cross-linking with riboflavin and UVA light]. / Kollagenvernetzung mit Riboflavin und UVA-Licht.

PURPOSE: Since 1998 collagen cross-linking is used for patients with progressive keratoconus. Today it can almost be considered as the standard therapy. METHODS: Patients with progressive keratoconus and minimal corneal thickness of 400 µm have been cross-linked within a study - (EK 310 499) approved by the ethical committee since 1998. An increase of the maximum K-value by ≥ 1 D within the last year, patient's statement of deteriorating visual acuity or the necessity of new contact len fitting more than once in 2 years were considered as progression. RESULTS: The analysis includes 153 eyes of 111 patients with a minimal follow-up of 12 months and a maximum follow-up of 6 years. The keratectasia significantly decreased in the 1 (st) year by 2.28 D. The visual acuity improved significantly by at least one line or, respectively, remained stable (i. e., no line loss) in the 1st year in 73 %. The results remained stable over the next two years. Despite the low number of patients with a follow-up longer than 3 years and therefore limited statistical statement power, our results still indicate a long-term stabilisation or, respectively, improvement after collagen cross-linking. We saw no severe side-effects. Three patients with an exacerbated neurodermitis showed continuous progression of keratoconus and were cross-linked again. CONCLUSIONS: To date there have been numerous promising publications on collagen cross-linking for keratoconus. The results of this study indicate that collagen cross-linking appears to be an effective therapeutic option for progressing keratoconus. Besides the clinical there are enormous economical and psychosocial benefits. Cross-linking is an out-patient, minimally-invasive, cost-effective treatment with minimal strain for the persons concerned.

Volumetric and semiquantitative assessment of MRI-detected subchondral bone marrow lesions in knee osteoarthritis: a comparison of contrast-enhanced and non-enhanced imaging.

OBJECTIVE: Aim was to compare volumetric and semi-quantitative (SQ) measurements of subchondral bone marrow lesions (BMLs) on non-fat-suppressed (FS) T1-weighted (w), T1-w FS contrast enhanced (CE) and proton density (PD)-w FS images in order to define which sequence depicts the lesions to their maximum extent and if T1-w FS CE images and PD-w FS images may be used interchangeably to assess BMLs in a volumetric or SQ fashion. DESIGN: Thirty-two patients with clinical knee osteoarthritis (OA) were scanned on a standard 1.5 T MRI system. A total of 47 BMLs were identified and were manually segmented on all three sequences. BMLs were also assessed semiquantitatively using the Whole Organ Magnetic Resonance Imaging Score (WORMS). The volumetric and SQ results were compared across the three imaging sequences using paired t-tests. RESULTS: Eighty-three percent of the lesions appeared largest on the PD-w FS sequence. Significant differences were observed for volumetric measurements between all three sequences (P < 0.001), however the mean volume difference between PD-w FS and T1-w FS CE (38%) was much smaller than for non-FS T1-w and PD-w FS/T1-w FS CE sequences (195% and 114%, respectively). Significant differences in WORMS scores were noted between PD-w FS and non-FS T1-w images and between T1-w FS CE and non-FS T1-w images (P < 0.001), but no significant difference was observed between PD-w FS and T1-w FS CE images. CONCLUSION: Our findings suggest that the T1-w FS CE and PD-w FS sequences may be interchangeably used for quantitative volumetric and SQ assessment of BMLs.

[Corneal scar development after cross-linking in keratoconus]. / Narbenbildung nach Hornhautvernetzung beim Keratokonus.

BACKGROUND: Corneal scar development after riboflavin-UVA-induced corneal collagen cross-linking (CXL) was retrospectively evaluated. PATIENTS AND METHODS: A total of 163 CXL-treated eyes in 127 patients with stage 1-3 keratoconus according to Krumeich's classification were included in this retrospective analysis. The follow-up period was 1 year. At the first and at all follow-up examinations uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), biomicroscopic findings, corneal topography and corneal thickness were recorded. RESULTS: At 1 year following CXL, 149 eyes (91.4%) of 114 patients had a clear cornea without corneal scar (control group), while 14 eyes (8.6%) of 13 patients developed clinically significant corneal scar (scar group). Preoperatively, the mean K value of the apex was 62.1 ± 13.8 D in the control group and 71.1 ± 13.2 D in the scar group (P=.02). The mean value of corneal thickness before the procedure was 478.1 ± 52.4 µm in the control group and 420.0 ± 33.9 µm in the scar group (P=.001). The UCVA and BCVA, which were preoperatively similar between groups (P=.59, P=.75 respectively), were postoperatively improved in the control group (P=.023, P=.001 respectively), but reduced in the scar group (P=.012, P=.004 respectively). CONCLUSION: K-values and corneal thickness could be considered as predictive factors for the possible development of corneal scarring after riboflavin-UVA-induced CXL. Advanced keratoconus appears to be associated with a higher risk of corneal scar development due to lower corneal thickness, greater curvature and intrinsic tissue characteristics.