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Increased drought intensity and frequency exposes soil bacteria to prolonged water stress. While numerous studies reported on behavioral and physiological mechanisms of bacterial adaptation to water stress, changes in bacterial cell surface properties during adaptation are not well researched. We studied adaptive changes in cell surface hydrophobicity (CSH) after exposure to osmotic (NaCl) and matric stress (polyethylene glycol 8000 [PEG 8000]) for six typical soil bacteria (Bacillus subtilis, Arthrobacter chlorophenolicus, Pseudomonas fluorescens, Novosphingobium aromaticivorans, Rhodococcus erythropolis, and Mycobacterium pallens) covering a wide range of cell surface properties. Additional physicochemical parameters (surface chemical composition, surface charge, cell size and stiffness) of B. subtilis and P. fluorescens were analyzed to understand their possible contribution to CSH development. Changes in CSH caused by osmotic and matric stress depend on strain and stress type. CSH of B. subtilis and P. fluorescens increased with stress intensity, R. erythropolis and M. pallens exhibited a generally high but constant contact angle, while the response of A. chlorophenolicus and N. aromaticivorans depended on growth conditions and stress type. Osmotically driven changes in CSH of B. subtilis and P. fluorescens are accompanied by increasing surface N/C ratio, suggesting an increase in protein concentration within the cell wall. Cell envelope proteins thus presumably control bacterial CSH in two ways: (i) by increases in the relative density of surface proteins due to efflux of cytoplasmic water and subsequent cell shrinkage, and (ii) by destabilization of cell wall proteins, resulting in conformational changes which render the surface more hydrophobic. IMPORTANCE Changes in precipitation frequency, intensity, and temporal distribution are projected to result in increased frequency and intensity of droughts and heavy rainfall events. Prolonged droughts can promote the development of soil water repellency (SWR); this impacts the infiltration and distribution of water in the soil profile, exposing soil microorganisms to water stress. Exposure to water stress has recently been reported to result in increased cell surface hydrophobicity. However, the mechanism of this development is poorly understood. This study investigates the changes in the physicochemical properties of bacterial cell surfaces under water stress as a possible mechanism of increased surface hydrophobicity. Our results improve understanding of the microbial response to water stress in terms of surface properties, the variations in stress response depending on cell wall composition, and its contribution to the development of SWR.

BackgroundWith the outbreak of COVID-19, government measures including social distancing and restrictions of social contacts were imposed to slow the spread of the virus. Since older adults are at increased risk of severe disease, they were particularly affected by these restrictions. These may negatively affect mental health by loneliness and social isolation, which constitute risk factors for depressiveness. We aimed to analyse the impact of perceived restriction due to government measures on depressive symptoms and investigated stress as mediator in an at-risk-population in Germany.MethodsData were collected in April 2020 from the population of the AgeWell.de-study, including individuals with a Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score ≥9, using the depression subscale of the Brief Symptom Inventory (BSI-18) and the Perceived Stress Scale (PSS-4). Feeling restricted due to COVID-19 government measures was surveyed with a standardized questionnaire. Stepwise multivariate regressions using zero-inflated negative binomial models were applied to analyse depressive symptoms, followed by a general structural equation model to assess stress as mediator. Analysis were controlled for sociodemographic factors as well as social support.ResultsWe analysed data from 810 older adults (mean age = 69.9, SD = 5). Feeling restricted due to COVID-19 government measures was linked to increased depressiveness (b = 0.19; p b = 0.04; p = 0.43), while stress was linked to increased depressive symptoms (b = 0.22; p b = 0.26; p ConclusionWe found evidence that feeling restricted due to COVID-19 government measures is associated with higher levels of depressive symptoms in older adults at increased risk for dementia. The association is mediated by perceived stress. Furthermore, social support was significantly associated with less depressive symptoms. Thus, it is of high relevance to consider possible adverse effects of government measures related to COVID-19 on mental health of older people.

Epidemiological data reveal that there is a need for prevention measures specifically targeted at children with low SES. In the German federal state Mecklenburg-Western Pomerania preschools in socially deprived regions can apply for additional funds to support children with developmental risks. Mandatory criteria for obtaining these funds involve an annual assessment of all children using the “Dortmunder Developmental Screening for Preschools (DESK 3–6 R).” This instrument can detect and monitor developmental risks in the domains fine motor skills, gross motor skills, language, cognition, and social development. In this study, we examine the domain “Attention and concentration,” which is included for the 5 to 6-year-old age group, using data from two consecutive survey waves (sw). Research questions: (1) Does the prevalence rate ratio (PRR) improve over time? (2) Is the rate of improvements (developmental risk at sw1, no developmental risk at sw2) higher than the rate of deteriorations (no developmental risk at sw1, developmental risk at sw2)? Prospective cohort analysis (n = 940). The prevalence rate of a developmental risk in this DESK domain decreases over time (PRR = 0.78; p = 0.019). The ratio of the rate of improvements is 8.47 times higher than the rate of deteriorations. The results provide evidence of the effectiveness of targeted intervention measures in preschools focusing on skills that improve attention and concentration. This is significant considering the small-time interval and the categorization method of DESK scores. Nevertheless, over the same time period, the DESK results of some children deteriorated. Therefore, preschools also have to be aware that it is natural for some children to show modest declines in their skills over time. German Clinical Trials Register, ID: DRKS00015134, Registered on 29 October 2018, retrospectively registered.

BackgroundOver the course of the COVID-19 pandemic, previous studies have shown that the physical as well as the mental health of children and adolescents significantly deteriorated. Future anxiety caused by the COVID-19 pandemic and its associations with quality of life has not previously been examined in school children.MethodsAs part of a cross-sectional web-based survey at schools in Mecklenburg-Western Pomerania, Germany, two years after the outbreak of the pandemic, school children were asked about COVID-19-related future anxiety using the German epidemic-related Dark Future Scale for children (eDFS-K). Health-related quality of life (HRQoL) was assessed using the self-reported KIDSCREEN-10. The eDFS-K was psychometrically analyzed (internal consistency and confirmatory factor analysis) and thereafter examined as a predictor of HRQoL in a general linear regression model.ResultsA total of N = 840 8–18-year-old children and adolescents were included in the analysis. The eDFS-K demonstrated adequate internal consistency reliability (Cronbach's α = 0.77), and the confirmatory factor analysis further supported the one-factor structure of the four-item scale with an acceptable model fit. Over 43% of students were found to have low HRQoL. In addition, 47% of the students sometimes to often reported COVID-19-related fears about the future. Children with COVID-19-related future anxiety had significantly lower HRQoL (B = – 0.94, p < 0.001). Other predictors of lower HRQoL were older age (B = – 0.63, p < 0.001), and female (B = – 3.12, p < 0.001) and diverse (B = – 6.82, p < 0.001) gender.ConclusionTwo years after the outbreak of the pandemic, school-aged children continue to exhibit low HRQoL, which is further exacerbated in the presence of COVID-19-related future anxiety. Intervention programs with an increased focus on mental health also addressing future anxiety should be provided.

Background Right ventricular outflow tract (RVOT) stenosis after repair of tetralogy of Fallot has been linked with favorable right ventricular remodeling but adverse outcomes. The aim of our study was to assess the hemodynamic impact and prognostic relevance of right ventricular pressure load in this population. Methods and Results A total of 296 patients with repaired tetralogy of Fallot (mean age, 17.8±7.9 years) were included in a prospective cardiovascular magnetic resonance multicenter study. Myocardial strain was quantified by feature tracking technique at study entry. Follow‐up, including the need for pulmonary valve replacement, was assessed. The combined end point consisted of ventricular tachycardia and cardiac death. A higher echocardiographic RVOT peak gradient was significantly associated with smaller right ventricular volumes and less pulmonary regurgitation, but lower biventricular longitudinal strain. During a follow‐up of 10.1 (0.1–12.9) years, the primary end point was reached in 19 of 296 patients (cardiac death, n=6; sustained ventricular tachycardia, n=2; and nonsustained ventricular tachycardia, n=11). A higher RVOT gradient was associated with the combined outcome (hazard ratio [HR], 1.03; 95% CI, 1.00–1.06; P =0.026), and a cutoff gradient of ≥25 mm Hg was predictive for cardiovascular events (HR, 3.69; 95% CI, 1.47–9.27; P =0.005). In patients with pulmonary regurgitation ≥25%, a mild residual RVOT gradient (15–30 mm Hg) was not associated with a lower risk for pulmonary valve replacement. Conclusions Higher RVOT gradients were associated with less pulmonary regurgitation and smaller right ventricular dimensions but were related to reduced biventricular strain and emerged as univariate predictors of adverse events. Mild residual pressure gradients did not protect from pulmonary valve replacement. These results may have implications for the indication for RVOT reintervention in this population.

Background Laparoscopic techniques have become the standard approach for most liver resections. Clinical studies providing conclusive evidence which patients benefit most from minimal-invasive surgery remain limited. Methods We retrospectively analyzed data of all consecutive cases of laparoscopic liver resection between 2015 and 2018 at our center. We compared patients with and without prior abdominal surgeries with respect to postoperative complications (Clavien-Dindo score), length of operation, length of ICU stay and length of hospitalization in univariate and multivariate analyses. Results Within the study period 319 patients underwent laparoscopic liver resections, 44% of which had a history of abdominal surgeries. Pre-operative characteristics were similar to patients without prior surgeries. Both groups showed comparable rates of post-operative complications (Clavien-Dindo score ≥3a; 12% in patients without vs. 16% with prior surgeries, p = 0,322). There were no significant differences in length of surgery or length of stay in the ICU or in the hospital. Conclusion Our data suggest that history of prior abdominal surgery is not a risk factor for post-operative complications after laparoscopic liver resection. We conclude that prior abdominal surgery should not be considered a contra-indication for laparoscopic approach in liver resection.

Summary Background Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. Methods The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5–15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints–erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4–6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov , NCT02573012 . Findings Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35–0·73) with tapered prednisone and −0·08 (–0·27 to 0·12) with continued prednisone (difference 0·61 [0·35–0·88]; p Interpretation In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. Funding F Hoffmann-La Roche.

Minimally invasive techniques have been broadly introduced to liver surgery during the last couple of years. In this study, we aimed to report the incidence and potential risk factors for incisional hernia (IH) as well as health-related quality of life (HRQoL) after laparoscopic liver resections (LLR). All patients undergoing LLR between January 2014 and June 2017 were contacted for an outpatient hernia examination. In all eligible patients, photo documentation of the scar was performed and IH was evaluated by clinical examination and by ultrasound. Patients also completed a questionnaire to evaluate IH-specific symptoms and HRQoL. Obtained results were retrospectively analyzed with regard to patients’ characteristics, perioperative outcomes and applied minimally invasive techniques, such as multi-incision laparoscopic liver surgery or hand-assisted/single-incision laparoscopic surgery (HALS/SILS). Of 184 patients undergoing surgery, 161 (87.5%) met the inclusion criteria and 49 patients (26.6%) participated in this study. After a median time of 26 months (range 19–50 months) after surgery, we observed an overall incidence of IH of 12%. Five of 6 patients were overweight or obese (BMI ≥ 25) and 5 of 6 hernias were located at the umbilical site. Univariate analysis suggested the performance status at time of operation (ASA score ≥ 3; HR 5.616, 95% CI 1.012–31.157, p = 0.048) and the approach (HALS/SILS, HR 6.571, 95% CI 1.097–39.379, p = 0.039) as potential risk factors for IH. A higher frequency of hernia-related physical restrictions (HRR; p = 0.058) and a decreased physical functioning (p = 0.17) were noted in patients with IH; however, both being short of statistical significance. Advantages of laparoscopic surgery with regard to low rates of IH can be translated to minimally invasive liver surgery. Even though there are low rates of IH, patients with poor performance status at the time of operation should be monitored closely. While patients’ characteristics are hard to influence, it might be worth focusing on surgical factors such as the approach and the closure of the umbilical site to further minimize the rate of IH.

Purpose To identify risk factors associated with the occurrence of complete uterine rupture (CUR) in comparison to partial uterine rupture (PUR) to further investigate to what extent a standardized definition is needed and what clinical implications can be drawn. Methods Between 2005 and 2017 cases with CUR and PUR at Charité University Berlin, Germany were retrospectively identified. Demographic, obstetric and outcome variables were analyzed regarding the type of rupture. Binary multivariate regression analysis was conducted to identify risk factors associated with CUR. In addition, the intended route of delivery (trial of labor after cesarean delivery (TOLAC) and elective repeat cesarean delivery (ERCD)), divided according to the type of rupture, was compared. Results 92 cases with uterine rupture were identified out of a total of 64.063 births (0.14%). Puerperal complications were more frequent in CUR (67.9 versus 41.1%, p = 0.021). Multiparity ≥ 3 was more frequent in CUR (31 versus 10.7%, p = 0.020). Factors increasing the risk for CUR were parity ≥ 3 (OR = 3.8, p = 0.025), previous vaginal birth (OR = 4.4, p = 0.011), TOLAC (OR = 6.5, p p = 0.036). After multivariate analysis, the only independent risk factor associated with CUR was TOLAC (OR = 7.4, p = 0.017). Conclusion TOLAC is the only independent risk factor for CUR. After optimized antenatal counselling TOLAC and ERCD had comparable short-term maternal and fetal outcomes in a high resource setting. A high number of previous vaginal births does not eliminate the risk of uterine rupture. A clear distinction between CUR and PUR is essential to ensure comparability among studies.

Overcoming the detrimental effects of sweet spots during crystallization is an important step to improve the quantitative abilities of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry. In this study, we introduce MALDI targets, which exhibit a channel design to reduce sweet spot phenomena and improve reproducibility. The size of the channels was 3.0 mm in length, 0.35 mm in depth, and 0.40 mm in width, adjusted to the width of the implemented laser beam. For sample deposition, the matrix/sample mixture was homogenously deposited into the channels using capillary action. To demonstrate the proof‐of‐principle, the novel plates were used for the quantification of acetyl‐L‐carnitine in human blood plasma using a combined standard addition and isotope dilution method. The results showed that the reproducibility of acetyl‐L‐carnitine detection was highly improved over a conventional MALDI‐MS assay, with RSD values of less than 5.9% in comparison with 15.6% using the regular MALDI method. The limits of quantification using the new plates were lowered approximately two‐fold in comparison with a standard rastering approach on a smooth stainless‐steel plate. Matrix effects were also assessed and shown to be negligible. The new assay was subsequently applied to the quantification of acetyl‐L‐carnitine in human plasma samples.

Introduction: With the increased emergence of SARS-CoV-2 variants, the impact on schools and preschools remains a matter of debate. To ensure that schools and preschools are kept open safely, the identification of factors influencing the extent of outbreaks is of importance.Aim: To monitor dynamics of COVID-19 infections in schools and preschools and identify factors influencing the extent of outbreaks.Methods: In this prospective observational study we analyzed routine surveillance data of Mecklenburg-Western Pomerania, Germany, from calendar week (CW) 32, 2020 to CW19, 2021 regarding SARS-CoV-2 infection events in schools and preschools considering changes in infection control measures over time. A multivariate linear regression model was fitted to evaluate factors influencing the number of students, teachers and staff tested positive following index cases in schools and preschools. Due to an existing multicollinearity in the common multivariate regression model between the variables “face mask obligation for children” and “face mask obligation for adults”, two further separate regression models were set up (Multivariate Model Adults and Multivariate Model Children).Results: We observed a significant increase in secondary cases in preschools in the first quarter of 2021 (CW8 to CW15, 2021), and simultaneously a decrease in secondary cases in schools. In multivariate regression analysis, the strongest predictor of the extent of the outbreaks was the teacher/ caregiver mask obligation (B = −1.9; 95% CI: −2.9 to −1.0; p < 0.001). Furthermore, adult index cases (adult only or child+adult combinations) increased the likelihood of secondary cases (B = 1.3; 95% CI: 0.9 to 1.8; p < 0.001). The face mask obligation for children also showed a significant reduction in the number of secondary cases (B = −0.6; 95% CI: −0.9 to −0.2; p = 0.004.Conclusion: The present study indicates that outbreak events at schools and preschools are effectively contained by an obligation for adults and children to wear face masks.

The current risk of infection with SARS-CoV-2 in schools continues to be a subject of controversy."schugi-MV" collects data on the incidence of infection, hygiene management and other factors in structured inspections of schools in Mecklenburg-Western Pomerania. Recommendations for safe teaching are to be derived from the results. This article presents information on the first 10 schools visited between 18.12.2020 and 20.01.2021.At the schools visited, the ratio of the number of index cases among adults and children was 1:1.25. The inspections showed a great heterogeneity of schools and school buildings and the resulting possibilities for implementing infection control measures.Based on the present preliminary results, hygiene and infection control measures at schools in Mecklenburg-Western Pomerania cannot be standardised, but should leave room for design.Die aktuelle Infektionsgefahr mit SARS-CoV-2 in Schulen wird weiterhin kontrovers diskutiert.„schugi-MV“ erfasst in strukturierten Begehungen von Schulen in Mecklenburg-Vorpommern (M-V) Daten zum Infektionsgeschehen, Hygienemanagement sowie weiteren Faktoren. Aus den Ergebnissen sollen Empfehlungen für einen sicheren Unterricht abgeleitet werden. In diesem Artikel werden Informationen zu den ersten 10, zwischen dem 18.12.2020 und 20.01.2021 besuchten Schulen vorgestellt.An den besuchten Schulen lag das Verhältnis der Anzahl Indexfälle bei Erwachsenen und Kindern bei 1:1,25. Die Begehungen zeigten eine große Heterogenität der Schulen und Schulgebäude sowie der dadurch bedingten Möglichkeiten zur Umsetzung von Infektionsschutzmaßnahmen.Basierend auf den vorliegenden, vorläufigen Ergebnissen sind Hygiene- und Infektionsschutzmaßnahmen an den Schulen in M-V nicht standardisierbar, sondern sollten Gestaltungsspielraum lassen.

Background and Objectives: In children, hepatoblastoma preferentially is managed by liver resection (LR). However, in irresectable cases, liver transplantation (LT) is required. The aim of our study was to compare short- and long-term results after LR and LT for the curative treatment of hepatoblastoma. Materials and Methods: Retrospective analysis of all patients treated surgically for hepatoblastoma from January 2000 until December 2019 was performed. Demographic and clinical data were collected before and after surgery. The primary endpoints were disease free survival and patient survival. Results: In total, 38 patients were included into our analysis (n = 28 for LR, n = 10 for LT) with a median follow-up of 5 years. 36 patients received chemotherapy prior to surgery. Total hospital stay and intensive care unit (ICU) stay were significantly longer within the LT vs. the LR group (ICU 23 vs. 4 days, hospital stay 34 vs. 16 days, respectively, p &lt, 0.001). Surgical complications (≤Clavien–Dindo 3a) were equally distributed in both groups (60% vs. 57%, p = 1.00). Severe complications (≥Clavien–Dindo 3a) were more frequent after LT (50% vs. 21.4%, p = 0.11). Recurrence rates were 10.7% for LR and 0% for LT at 5 years after resection or transplantation (p = 0.94). Overall, 5-year survival was 90% for LT and 96% for LR (p = 0.44). Conclusions: In irresectable cases, liver transplantation reveals excellent outcomes in children with hepatoblastoma with an acceptable number of perioperative complications.

BackgroundSince the onset of the COVID-19 pandemic, children have been mentally and physically burdened, particularly due to school closures, with an associated loss of learning. Therefore, efficient testing strategies with high sensitivity are necessary to keep schools open. Apart from individual rapid antigen testing, various methods have been investigated, such as PCR-based pool-testing of nasopharyngeal swabs, gargle, or saliva samples. To date, previous validation studies have found the PCR-based saliva swab pool testing method to be an effective screening method, however, the acceptability and feasibility of a widespread implementation in the school-setting among stakeholders has not been comprehensively evaluated.MethodsIn this pilot study, SARS-CoV-2 saliva swab pool testing of up to 15 swabs per pool was conducted in ten primary and special schools in Mecklenburg-Western Pomerania, Germany, over a period of one month. Thereafter, parents, teachers and school principals of the participating schools as well as the participating laboratories were surveyed about the feasibility and acceptability of this method, its large-scale implementation and challenges. Data were analyzed quantitatively and qualitatively.ResultsDuring the study period, 1,630 saliva swab pools were analyzed, of which 22 tested SARS-CoV-2 positive (1.3%). A total ofN= 315 participants took part in the survey. Across all groups, the saliva swab pool testing method was perceived as more child-friendly (>87%), convenient (>82%), and easier (>81%) compared to rapid antigen testing by an anterior nasal swab. Over 80% of all participants favored widespread, regular use of the saliva swab method.ConclusionIn school settings in particular, a high acceptability of the test method is crucial for a successful SARS-CoV-2 surveillance strategy. All respondents clearly preferred the saliva swab method, which can be used safely without complications in children six years of age and older. Hurdles and suggestions for improvement of an area-wide implementation were outlined.

Background While laparoscopic liver surgery has become a standard procedure, experience with robotic liver surgery is still limited. The aim of this prospective study was to evaluate safety and feasibility of robotic liver surgery and compare outcomes with conventional laparoscopy. Methods We here report the results of a single-center, prospective, post-marketing observational study (DRKS00017229) investigating the safety and feasibility of robotic liver surgery. Baseline characteristics, surgical complexity (using the IWATE score), and postoperative outcomes were then compared to laparoscopic liver resections performed at our center between January 2015 and December 2020. A propensity score-based matching (PSM) was applied to control for selection bias. Results One hundred twenty nine robotic liver resections were performed using the da Vinci Xi surgical system (Intuitive) in this prospective study and were compared to 471 consecutive laparoscopic liver resections. After PSM, both groups comprised 129 cases with similar baseline characteristics and surgical complexity. There were no significant differences in intraoperative variables, such as need for red blood cell transfusion, duration of surgery, or conversion to open surgery. Postoperative complications were comparable after robotic and laparoscopic surgery (Clavien–Dindo ≥ 3a: 23% vs. 19%, p = 0.625); however, there were more bile leakages grade B–C in the robotic group (17% vs. 7%, p = 0.006). Length of stay and oncological short-term outcomes were comparable. Conclusions We propose robotic liver resection as a safe and feasible alternative to established laparoscopic techniques. The object of future studies must be to define interventions where robotic techniques are superior to conventional laparoscopy.

Background In recent years, laparoscopic liver resection has elicited growing attention as a safe procedure for various forms of hepatic resection. In the context of an aging population, this study aims to evaluate outcomes in elderly patients (>70 y) compared with younger patients (≤70 y). Methods All consecutive patients undergoing minimally invasive liver resections between December 2013 and January 2018 at the Department of Surgery, Charite–Universitatsmedizin Berlin, were included in this analysis. Patients’ characteristics, such as body mass index, American Society of Anesthesiologists classification, as well as underlying liver disease and function, were examined and the perioperative outcomes of patients aged >70 y (group 1; G1) contrasted with patients aged ≤ 70 y (group 2; G2). Results Of 250 patients, 67 were >70 y old (G1) and 183 were ≤70 y old (G2). Patients in G1 were characterized by a higher body mass index (27.6 kg/m2 versus 24.9 kg/m2; P = 0.004) and impaired physical states (American Society of Anesthesiologists score III/IV; 60% versus 37%; P = 0.002) when compared with group 2. G1 also exhibited higher rates of primary and secondary hepatic malignancies (G1: n = 62; 92.5%; G2: n = 115, 62.8%; P = 0.031) in addition to higher rates of cirrhosis (G1: n = 30, 44.8%; G2: n = 38, 20.8%; P = Conclusions Minimally invasive liver resection is a feasible and safe procedure in elderly patients despite this age group exhibiting a higher rate of primary and secondary malignancy and cirrhosis, as well as an overall more severely compromised physical health when compared with patients under the age of 70 y. Therefore, it stands to reason that patients in poorer general health might particularly benefit from a minimally invasive approach.

OBJECTIVE We aimed to provide a comprehensive overview of the role of self-esteem in the treatment of patients with anorexia nervosa (AN). Specifically, our objectives were to investigate the differences in self-esteem between individuals with AN and healthy controls, or individuals with other eating disorders, and to examine self-esteem as an outcome, predictor, moderator, and mediator in AN treatment. METHOD The databases PsycINFO, PSYNDEXplus, Ovid MEDLINE®, and ProQuest were searched for studies published from 1990 to 2018. To estimate aggregated effect sizes, we performed random-effects meta-analyses. RESULTS A screening of 1,596 abstracts and 203 full-texts identified 68 relevant publications. Results suggest a significantly lower global self-esteem in individuals with AN than in healthy controls (d = -1.90, p

International audience; Aluminum (Al) is one of the most common elements in the earth crust and increasingly used in food, consumer products and packaging. Its hazard potential for humans is still not completely understood. Besides the metallic form, Al also exists as mineral, including the insoluble oxide, and in soluble ionic forms. Representatives of these three species, namely a metallic and an oxidic species of Al-containing nanoparticles and soluble aluminum chloride, were applied to human intestinal cell lines as models for the intestinal barrier. We characterized physicochemical particle parameters, protein corona composition, ion release and cellular uptake. Different in vitro assays were performed to determine potential effects and molecular modes of action related to the individual chemical species. For a deeper insight into signaling processes, microarray transcriptome analyses followed by bioinformatic data analysis were employed. The particulate Al species showed different solubility in biological media. Metallic Al nanoparticles released more ions than AlO nanoparticles, while AlCl showed a mixture of dissolved and agglomerated particulate entities in biological media. The protein corona composition differed between both nanoparticle species. Cellular uptake, investigated in transwell experiments, occurred predominantly in particulate form, whereas ionic Al was not taken up by intestinal cell lines. Transcellular transport was not observed. None of the Al species showed cytotoxic effects up to 200 µg Al/mL. The transcriptome analysis indicated mainly effects on oxidative stress pathways, xenobiotic metabolism and metal homeostasis. We have shown for the first time that intestinal cellular uptake of Al occurs preferably in the particle form, while toxicological effects appear to be ion-related.

While minimally invasive liver surgery has been increasingly adopted at least for minor resections, experience with robotic liver surgery is still limited to a few highly specialized centers. Due to the fear of abdominal adhesions, a history of prior surgeries is still used as an argument for open approaches.Clinical data of all consecutive robotic resections at our center, using the da Vinci Xi surgical system, between April, 2018 and December, 2020, were collected and analyzed as part of a prospective, post-marketing observational study (DRKS00017229). Prior abdominal surgeries were specified according to the surgical approach and localization. Baseline and perioperative outcome criteria were compared between patients with prior surgeries (PS) and patients with no prior surgeries (NPS) in univariate and multivariate analyses.Out of the 126 patients undergoing robotic liver resections, 59% had a history of abdominal surgeries, which were most often colorectal resections (28%) followed by liver resections (20%). Patients with NPS were more likely to undergo robotic liver resection for hepatocellular carcinoma or benign tumors, and to have underlying liver cirrhosis when compared to patients with PS. Other baseline characteristics as well as the extent of resections were similar. Duration of surgery (258 min), conversion rates (6%), and postoperative complications rates (21% Clavien-Dindo ≥ 3) showed no differences between NPS and PS. A subgroup of patients with a history of prior liver surgery showed a longer duration of surgery in univariate analysis. However, this was not confirmed in multivariate analysis which instead revealed tumor entity and liver cirrhosis as independently correlated with duration of surgery.We propose robotic liver resection to be safe and feasible, including in patients with prior abdominal surgeries. Each patient should be evaluated for a minimally invasive procedure regardless of a history of previous operations.

The trace element selenium (Se) is taken up from the diet and is metabolized mainly by hepatocytes. Selenoprotein P (SELENOP) constitutes the liver-derived Se transporter. Biosynthesis of extracellular glutathione peroxidase (GPx3) in kidney depends on SELENOP-mediated Se supply. We hypothesized that peri-operative Se status may serve as a useful prognostic marker for the outcome in patients undergoing liver transplantation due to hepatocellular carcinoma. Serum samples from liver cancer patients were routinely collected before and after transplantation. Concentrations of serum SELENOP and total Se as well as GPx3 activity were determined by standardized tests and related to survival, etiology of cirrhosis/carcinoma, preoperative neutrophiles, lymphocytes, thyrotropin (TSH) and Child-Pugh and Model for End-Stage Liver Disease (MELD) scores. A total of 221 serum samples from 79 transplanted patients were available for analysis. The Se and SELENOP concentrations were on average below the reference ranges of healthy subjects. Patients with ethanol toxicity-dependent etiology showed particularly low SELENOP and Se concentrations and GPx3 activity. Longitudinal analysis indicated declining Se concentrations in non-survivors. We conclude that severe liver disease necessitating organ replacement is characterized by a pronounced Se deficit before, during and after transplantation. A recovering Se status after surgery is associated with positive prognosis, and an adjuvant Se supplementation may, thus, support convalescence.

Altered pupillary function may reflect nonconvulsive status epilepticus (NCSE). Neurological pupil index (NPi) assessed by automated pupillometry is a surrogate marker of global pupillary function. We aimed to assess NPi changes in relation to NCSE treatment response. In this prospective observational study, serial automated pupillometry was performed in 68 NCSE episodes. In accordance with local standards, patients were treated with clonazepam (1–2 mg), levetiracetam (40 mg/kg), and lacosamide (5 mg/kg) in a stepwise approach under continuous electroencephalography monitoring until NCSE was terminated. Patients with refractory NCSE received individualized regimens. NPi was assessed bilaterally before and after each treatment step. For statistical analysis, the lower NPi of both sides (minNPi) was used. Nonparametric testing for matched samples and Cohen’s d to estimate effect size were performed. Principal component analysis was applied to assess the contribution of baseline minNPi, age, sex, and NCSE duration to treatment outcome. In 97.1% of 68 episodes, NCSE could be terminated; in 16.2%, NCSE was refractory. In 85.3% of episodes, an abnormal baseline minNPi ≤ 4.0 was obtained. After NCSE termination, minNPi increased significantly (p

Background Emerging evidence highlights the importance of preoperative expectations in predicting patient-reported outcomes of orthopedic surgeries. To date, it is still a matter of controversy whether patient satisfaction can be maximized by promoting either optimistic or realistic outcome expectations before surgery. Adjusting overly optimistic outcome expectancies in favor of a more realistic outlook on the limitations of total hip arthroplasty could reduce the risk of disappointment and lead to greater satisfaction with surgery outcomes. Our prospective cohort study was aimed at comparing the relative predictive influence of baseline expectations, expectation fulfillment and symptomatic improvement on the global effectiveness of total hip arthroplasty. Methods Ninety patients (49 female, 41 male; mean age: 63 ± 12.87 years) fulfilled inclusion criteria and completed a comprehensive preoperative assessment comprising sociodemographic, clinical, functional and psychological phenotypes. Moreover, the strengths of preoperative expectations for improvements in eight pain-related and functional domains were recorded on a 5-point Likert-scale. At 12 months after surgery, patients were asked to rate perceived improvements in each of these domains as well as the global effectiveness of the total hip replacement on a 5-point Likert-scale. To evaluate the relative impact of preoperative expectations, symptom improvement and the fulfillment of expectations on the global effectiveness of surgery, a sequential multiple regression analysis was performed. Results Compared with the actual improvement at 12-months follow-up, prior expectations had been overly optimistic in about 28% of patients for hip pain, in about 45% for walking ability and around 60% for back pain, independence in everyday life, physical exercise, general function social interactions and mental well-being. An optimistic hip pain expectation, walking ability at baseline and the fulfillment of expectations for walking ability, general function and independence in everyday life were found to independently predict global effectiveness ratings. Conclusions Positive expectation about pain and the fulfillment of expectations concerning functional domains predicted higher global effectiveness ratings. In line with many authors investigating the relationship between the fulfillment of expectations and satisfaction with medical interventions, we suggest that professionals should explicitly address their patients’ expectations during the preoperative education and consultation.

The mixed lineage leukemia 3 or MLL3 is the enzyme in charge of the writing of an epigenetic mark through the methylation of lysine 4 from the N-terminal domain of histone 3 and its deregulation has been related to several cancer lines. An interesting feature of this enzyme comes from its regulation mechanism, which involves its binding to an activating dimer before it can be catalytically functional. Once the trimer is formed, the reaction mechanism proceeds through the deprotonation of the lysine followed by the methyl-transfer reaction. Here we present a detailed exploration of the activation mechanism through a QM/MM approach focusing on both steps of the reaction, aiming to provide new insights into the deprotonation process and the role of the catalytic machinery in the methyl-transfer reaction. Our finding suggests that the source of the activation mechanism comes from conformational restriction mediated by the formation of a network of salt-bridges between MLL3 and one of the activating subunits, which restricts and stabilizes the positioning of several residues relevant for the catalysis. New insights into the deprotonation mechanism of lysine are provided, identifying a valine residue as crucial in the positioning of the water molecule in charge of the process. Finally, a tyrosine residue was found to assist the methyl transfer from SAM to the target lysine., Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica

BACKGROUND Current literature about the effects of patients' expectations on relevant outcome measures is still conflicting and incomplete. The aim of this prospective observational study was to assess the influence of expectations and the fulfillment of expectations on postoperative pain intensity and pain relief. Furthermore, clinical characteristics influencing expectations and the fulfillment of expectations were explored. METHODS Patients undergoing elective orthopedic surgery were assessed using two standardized self-report questionnaires on the day before surgery and the third postoperative day. One hundred and seventy patients from 21 to 93 years (average age 64.6, SD 14.0 years; 55% female) were consecutively included. RESULTS While expectations of pain intensity did not correlate with pain experience after surgery, the fulfillment of expectations was associated with postoperative pain experience. Patients whose expectations were fulfilled were found to be more satisfied with the overall treatment as compared to those whose expectations were not fulfilled. Higher levels of expected pain were associated with higher fear of surgery and fear of postoperative pain. Preoperative pain intensity, length of treatment before the surgery, fear of surgery, helplessness and fear of postoperative pain were associated with higher postoperative pain intensity. Lower levels of preoperative fear of surgery and fear of postoperative pain were found to correlate with the fulfillment of pain relief. CONCLUSIONS Our study indicates that postoperative pain and satisfaction with the treatment are associated with the degree of fulfillment of expectations rather than the expected pain itself.

Background: Despite recent advances in the field of laparoscopic liver surgery, intrahepatic cholangiocarcinoma (iCC) as an entity has been nearly exempted from the new approaches because of propos...

Abdominal wall closure after pediatric liver transplantation (pLT) in infants may be hampered by graft-to-recipient size discrepancy. Herein, we describe the use of a porcine dermal collagen acellular graft (PDCG) as a biological mesh (BM) for abdominal wall closure in pLT recipients. Patients

The implications of multi-incision (MILS) and hand-assisted (HALS) laparoscopic techniques for minimally invasive liver surgery with regard to perioperative outcomes are not well defined. The purpose of this study was to compare MILS and HALS using propensity score matching. 309 patients underwent laparoscopic liver resections (LLR) between January 2013 and June 2018. Perioperative outcomes were analyzed after a 1:1 propensity score match. Subgroup analyses of matched groups, i.e., radical lymphadenectomy (LAD) as well as resections of posterosuperior segments (VII and/or VIII), were performed. MILS was used in 187 (65.2%) and HALS in 100 (34.8%) cases, with a significant decrease of HALS resections over time (p = 0.001). There were no significant differences with regard to age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) Score, previous abdominal surgery and cirrhosis between both groups. Patients scheduled for HALS were characterized by a significantly higher rate of malignant tumors (p

Chronic pain is a frequent comorbidity of patients in hospitals and has an influence on the clinical course and the duration of hospitalization. There is a need to have a better understanding of chronic pain as a comorbidity and it should be considered to a greater extent in understanding diseases, in treatment concepts and hospital structures to ensure a resource-oriented and high-quality care. This begins on admission by identifying pre-existing pain and related risk factors with the medical history and taking these into account in the treatment regimen. A multimodal treatment approach that involves medicinal, educational, psychological and physiotherapeutic expertise is required in these patients. A unimodal approach in the treatment is not effective. A pain physician should be involved in the treatment team as early as possible. Furthermore, psychological joint supervision should be available for these patients as several studies have demonstrated positive perioperative effects of psychological approaches on the treatment in this patient group.

The hexapeptide hIAPP22–27 (NFGAIL) is known as a crucial amyloid core sequence of the human islet amyloid polypeptide (hIAPP) whose aggregates can be used to better understand the wild‐type hIAPP′s toxicity to β‐cell death. In amyloid research, the role of hydrophobic and aromatic‐aromatic interactions as potential driving forces during the aggregation process is controversially discussed not only in case of NFGAIL, but also for amyloidogenic peptides in general. We have used halogenation of the aromatic residue as a strategy to modulate hydrophobic and aromatic‐aromatic interactions and prepared a library of NFGAIL variants containing fluorinated and iodinated phenylalanine analogues. We used thioflavin T staining, transmission electron microscopy (TEM) and small‐angle X‐ray scattering (SAXS) to study the impact of side‐chain halogenation on NFGAIL amyloid formation kinetics. Our data revealed a synergy between aggregation behavior and hydrophobicity of the phenylalanine residue. This study introduces systematic fluorination as a toolbox to further investigate the nature of the amyloid self‐assembly process., F for formation: This study introduces systematic fluorination as a tool to investigate the nature of amyloid formation as shown for the model peptide NFGAIL. Modulation of hydrophobicity and the σ‐framework of the Phe residue trough fluorine and iodine led to different amyloid folding kinetics. TEM and SAXS studies revealed the presence of amyloid fibrils.

Background and Aim: In recent years, minimally invasive surgical approaches have gained an increasingly important role in hepatobiliary surgery. The aim of this study was to investigate th...

Summary Objective Recently, water jet-assisted liposuction (WAL) was successfully applied by several other authors to remove fat and induce skin contraction in nonfacial body areas. Extending the range of indications for this new method, the authors of this article report on their first experience with its use in facial contouring, fat harvesting, and hydrodissection of the facial skin flap in rhytidectomy in a case series of 25 patients. Methods Twenty-five patients (median age: 56 years) had facelift surgery under sedation, and the WAL technique was used for facial contouring, fat harvesting for facial lipotransfer, and hydrodissection of the facial skin flap. Patients were monitored for discomfort during the procedure. Complications such as bleeding, postoperative swelling, and hematoma formation were observed during a 1-week follow-up period, and intensity was rated by two independent surgeons using a special grading system. Furthermore, a patient survey (FACE-Q) was performed to analyze the patients' satisfaction and perception of the postsurgical esthetic results. Results The WAL technique can be applied under intravenous sedation without causing any discomfort in all treated patients [mean 1.16, standard deviation (SD) 0.31]. Intraoperative bleeding during WAL-assisted facial dissection was judged as not present at all times (mean 1.3, SD 0.32). Postoperative swelling (day 1: mean 1.82, SD 0.28; day 7: mean 1.18, SD 0.28) and hematoma formation following surgery (day 1: mean 1.58, SD 0.34; day 7: mean 1.18, SD 0.31) were judged as minor in all cases. Overall, no skin necrosis was detected. There was no need for revision surgery. More than half of our treated patients (n = 13) answered the FACE-Q questionnaire, verifying a high satisfaction rate with beneficial treatment results without the occurrence of any major complications. Conclusions The WAL technique seems to offer a safe and efficient treatment approach for facial contouring, facial fat harvesting, and simultaneous facial flap hydrodissection with only minor postoperative swelling and hematoma formation. Therefore, the authors believe that the WAL technique is a powerful and useful tool and should be used in modern facial plastic surgery.

Background Freehand ventricular catheter placement may represent limited accuracy for the surgeon's intent to achieve primary optimal catheter position. Objective To investigate the accuracy of a ventricular catheter guide assisted by a simple mobile health application (mhealth app) in a multicenter, randomized, controlled, simple blinded study (GAVCA study). Methods In total, 139 eligible patients were enrolled in 9 centers. Catheter placement was evaluated by 3 different components: number of ventricular cannulation attempts, a grading scale, and the anatomical position of the catheter tip. The primary endpoint was the rate of primary cannulation of grade I catheter position in the ipsilateral ventricle. The secondary endpoints were rate of intraventricular position of the catheter's perforations, early ventricular catheter failure, and complications. Results The primary endpoint was reached in 70% of the guided group vs 56.5% (freehand group; odds ratio 1.79, 95% confidence interval 0.89-3.61). The primary successful puncture rate was 100% vs 91.3% (P = .012). Catheter perforations were located completely inside the ventricle in 81.4% (guided group) and 65.2% (freehand group; odds ratio 2.34, 95% confidence interval 1.07-5.1). No differences occurred in early ventricular catheter failure, complication rate, duration of surgery, or hospital stay. Conclusion The guided ventricular catheter application proved to be a safe and simple method. The primary endpoint revealed a nonsignificant improvement of optimal catheter placement among the groups. Long-term follow-up is necessary in order to evaluate differences in catheter survival among shunted patients.

Knowledge on the change process in the treatment of anorexia nervosa (AN) is an important starting point for the improvement of treatment, yet very little evidence exists. In an exploratory analysis, we aimed to investigate the interdependencies between higher-rank change process factors, BMI and AN-specific cognitions and behaviours over the course of inpatient treatment.We included 176 female adult AN inpatients from three specialized centres. The temporal interdependencies between the change factors and the outcome variables over the course of treatment (t0: beginning, t1: mid-treatment, t2: end) were investigated using a path model.The sample had a mean age of 27.1 years (SD = 8.9 years) and a mean BMI at admission of 15.0 kg/mThe results are discussed with respect to the self-determination theory and the consistency theory. Further research on the change process in AN treatment is recommended.

A growing body of evidence indicates the role of melatonin (MT) in the pathogenesis of multiple sclerosis (MS): It modulates immune function, alleviates oxidative stress and it is linked to seasonality of MS relapse. This report addresses the potential clinical relevance of circadian MT rhythms in relapsing-remitting MS (RRMS) patients. The study sample comprised of fifty-five RRMS patients and fifty age- and sex-matched healthy control (HC) subjects. Circadian salivary MT was measured non-invasively at 12 time points over day in participants' home environment. 6-Hydroxy-melatoninsulfate (MT sulfate) concentration in night-time urine was assessed as an estimate for nocturnal MT. Ratings for neurological disability, health-related quality of life (HrQoL), fatigue, depressive symptoms and sleep patterns were additionally obtained. There was no evidence for an overall disturbed MT rhythm in RRMS patients. However, lower MT levels within the first hour after awakening were associated with longer disease duration. MT levels only correlated moderately with neurological disability. Sleep disruptions were more common in patients than in controls and were associated with lower nocturnal MT sulfate levels. MT also correlated moderately with fatigue and HrQoL. We did not find evidence for a generally disturbed circadian MT rhythm in RRMS patients but longer disease duration was associated with significantly lower MT levels. Moreover, MT correlated with a series of clinical features. The exact nature of this relationship remains unclear and future studies are needed in order to determine whether MT could serve as a potential therapeutic target in MS. KEY MESSAGES: Melatonin acts as a free radical scavenger and modulates immune function. In multiple sclerosis, low melatonin levels were associated with acute exacerbations. Melatonin levels are not generally disturbed in multiple sclerosis patients. But lower levels are associated with disease duration and clinical aspects. Salivary melatonin after awakening might serve as a good measure of melatonin.

Cost efficiency is important for hospitals in order to provide high-quality health care for all patients. As hemihepatectomies are increasingly being performed laparoscopically, the aims of this study were to evaluate the costs of laparoscopic hemihepatectomy and to compare them to conventional open techniques. This is a retrospective analysis of clinical outcomes and financial calculations of all patients who underwent hemihepatectomy between January 2015 and December 2016 at the Department of Surgery, Campus Charite Mitte and Campus Charite Virchow-Klinikum, Berlin, Germany, being allocated to the DRG (diagnosis-related group) H01A (complex operations of the liver and pancreas with complex intensive care treatment) or H01B (operations of the liver and pancreas without complex intensive care treatment). To overcome selection bias, a 1:1 propensity score matching (PSM) analysis was performed. After PSM, a total of 64 patients were identified; 32 patients underwent laparoscopic hemihepatectomy (LH); and 32 patients received open hemihepatectomy (OH). After PSM, no significant differences were observed in clinical baseline characteristics. The duration of surgery was significantly longer for patients undergoing LH compared to OH (LH, 334 min, 186–655 min; OH, 274 min, 176–454 min; p = 0.005). Patients in the LH group had a significantly shortened median hospital stay of 5 d, when compared to OH (LH, 9.5 d, 3–35 d; OH, 14.5 d, 7–37d; p = 0.005). We observed a significant higher rate of postoperative complication in the OH group (p = 0.022). Cost analysis showed median overall costs of 17,369.85€ in the LH group and 16,103.64€ in the OH group (p = 0.390). Our data suggest that higher intraoperative costs of laparoscopic liver surgery, e.g., for surgical devices and due to longer operation times, are compensated by fewer postoperative complications and consecutive shorter length of stay when compared with OH.

Background Due to the current poaching crisis in Africa, increasing numbers of white rhinoceroses (Ceratotherium simum) require opioid immobilisation for medical interventions or management procedures. Alarmingly, the results of both blood gas analysis and pulse oximetry regularly indicate severe hypoxaemia. Yet, the recovery of the animals is uneventful. Thus, neither of the techniques seems to represent the real oxygenation level. We hypothesized that unusual haemoglobin characteristics of this species interfere with the techniques developed and calibrated for the use in human patients. Methods Haemoglobin was isolated from blood samples of four adult, white rhinoceroses. Oxygen dissociation curves at pH 7.2 and 7.4 (37°C) were determined based on the absorbance change of haemoglobin in the Soret-region (around 420 nm). Absorbance spectra of oxy- and deoxyhaemoglobin extending into the infrared region were measured. Results Oxygen dissociation curves of rhinoceros haemoglobin showed the typical high oxygen affinity (p50 of 2.75 ± 0.07 and 2.00 ± 0.04 kPa for pH 7.2 and 7.4, respectively) under near-physiological conditions with respect to pH, temperature and DPG. The infrared absorbance spectra of oxy- and deoxyhaemoglobin showed only marginal deviations from standard human spectra, possibly due to the presence of a few percent of methaemoglobin in vitro. Conclusions Our data enables the development of a rhinoceros-specific blood gas analysis algorithm, which allows for species-specific calculation of SaO2 levels in anaesthetized animals. The inconspicuous absorbance spectra do not contribute to the systematic underestimation of SpO2 by pulse-oximetry.

In spite of convincing results from internationally prominent liver centres, laparoscopic liver surgery is not widely used in Germany. A structured program to develop laparoscopic liver surgery was established in 2015 at the Department of Surgery, Charité Hospital, Berlin, in order to provide support for establishing this approach in German hospitals.We now report the results of our centre for 250 consecutive laparoscopic liver resections between 12/2013 and 1/2018. A retrospective analysis was performed with respect to indications, patient characteristics, complexity of the operations and postoperative results. The development of the program was analysed by comparing period 1 (1/2014 - 12/2015) and period 2 (1/2016 - 12/2017).In comparison with period 1 (n = 16, 25% of patients), patients in period 2 (n = 75, 50% of patients) included a significantly greater percentage of patients with a high ASA score (3/4; p = 0.001). Hepatocellular carcinoma was the most frequent indication (n = 76, 30.4%), followed by colorectal liver metastases (n = 63, 25.2%). Malignant tumours increased over the years from 53.8% in period 1 to 75.7% in period 2 (p = 0.001). 72 major (≥ 3 segments) and 178 minor resections ( 3 segments) were performed, with an increase in major resections (n = 12, 17.9%) in period 1 to period 2 (n = 56, 33.1%, p = 0.02). In spite of the significantly higher percentage of complex operations in period 2, the rate of major complications (Dindo-Clavien ≥ III a) in period 2 was 16% (27 patients) was not significantly higher than in period 1, with 11.9% (8 patients, p = 0.432). 67 patients (26.8%) suffered from liver cirrhosis; the postoperative complication rate (Dindo-Clavien ≥ III a) was not significantly different between patients with (12%) and without cirrhosis (15.8%, p = 0.424).Aside from appropriate expertise in conventional open liver surgery, minimally invasive surgery and intraoperative sonography, it is necessary to develop a structured program for the reliable implementation of laparoscopic liver surgery in German hospitals. Because of the convincing results, conventional open liver surgery will be largely replaced in Germany by laparoscopic techniques in the coming years.Trotz überzeugender Ergebnisse international führender Leberzentren ist die laparoskopische Leberchirurgie in Deutschland weiterhin vergleichsweise wenig verbreitet. An der Chirurgischen Klinik der Charité – Universitätsmedizin Berlin wurde 2015 ein strukturiertes Programm zur Entwicklung der laparoskopischen Leberchirurgie etabliert, woraus sich mögliche Implikationen für die breite Etablierung an deutschen Kliniken ergeben.Wir berichten hier über unsere Zentrumserfahrungen aus 250 konsekutiven, laparoskopischen Leberresektionen zwischen 12/2013 und 1/2018. Es erfolgte eine retrospektive Auswertung in Hinblick auf Indikationen, Patientencharakteristika, Komplexität der Operationen und postoperative Ergebnisse. Die Entwicklung des Programmes wurde analysiert durch Vergleich des Zeitraumes 1 (1/2014 – 12/2015) und Zeitraumes 2 (1/2016 – 12/2017).Im Vergleich zum Zeitraum 1 (n = 16, 25% der Patienten) zeigte sich im Zeitraum 2 (n = 75, 50% der Patienten) ein signifikant höherer Prozentsatz von Patienten mit einem hohen ASA-Score (3/4; p = 0,001). Das hepatozelluläre Karzinom war die häufigste Indikation (n = 76, 30,4%), gefolgt von kolorektalen Lebermetastasen (n = 63, 25,2%), wobei sich über die Jahre eine Zunahme bösartiger Tumoren von 53,8% im Zeitraum 1 zu 75,7% im Zeitraum 2 (p = 0,001) zeigte. Es erfolgten 72 Major- (≥ 3 Segmente) und 178 Minorresektionen ( 3 Segmente) mit einer Zunahme an Majorresektionen vom Zeitraum 1 (n = 12, 17,9%) zum Zeitraum 2 (n = 56, 33,1%, p = 0,02). Trotz eines signifikant höheren Prozentsatzes an komplexen Eingriffen im Zeitraum 2 war die Rate an Majorkomplikationen (Dindo-Clavien ≥ III a) mit 16% (27 Patienten) nicht signifikant höher als im Zeitraum 1 mit 11,9% (8 Patienten, p = 0,432). 67 (26,8%) Patienten litten unter einer Leberzirrhose, wobei sich die postoperative Komplikationsrate (Dindo-Clavien ≥ III a) zwischen Patienten mit (12%) und ohne Zirrhose (15,8%) nicht signifikant unterschied (p = 0,424).Neben entsprechender Expertise in der konventionell offenen Leberchirurgie, in der minimalinvasiven Chirurgie und in der intraoperativen Sonografie ist ein strukturierter Aufbau eines Programmes notwendig, um die laparoskopische Leberchirurgie sicher an deutschen Kliniken zu implementieren. Aufgrund überzeugender Ergebnisse wird die konventionell offene Leberchirurgie in den nächsten Jahren auch in Deutschland durch laparoskopische Techniken weitestgehend abgelöst werden.

During the postpartum period, women are at higher risk of developing a mental disorder such as postpartum depression (PPD), a disorder that associates with mother-infant bonding and child development. Oxytocin is considered to play a key role in mother-infant bonding and social interactions and altered oxytocin plasma concentrations were found to be associated with PPD. In the present study, we evaluated oxytocin plasma levels and depressive symptoms during pregnancy and the postpartum period in healthy women. We evaluated 100 women twice during pregnancy (weeks 35 and 38) and three times in the postpartum period (within 2 days and 7 weeks and 6 months after delivery) by measuring oxytocin plasma levels with enzyme-linked immunosorbent assay (ELISA) and assessing depressive symptoms with the Montgomery-Asberg Depression Rating Scale. Oxytocin plasma levels significantly increased from the 35th week of gestation to 6 months postpartum in all women. However, levels decreased from the 38th week of gestation to 2 days after delivery in participants with postpartum depressive symptoms, whereas they continuously increased in the group without postpartum depressive symptoms; the difference between the course of oxytocin levels in the two groups was significant (Δt2-t3: t = 2.14; p = 0.036*). Previous depressive episodes and breastfeeding problems predicted postpartum depressive symptoms. Our results indicate that alterations in the oxytocin system during pregnancy might be specific for women who develop postpartum depressive symptoms. Future studies should investigate whether oxytocin plasma levels might have predictive value in women at high risk for PPD.

Introduction In a single-center, prospective, randomized clinical trial three different configured wound dressings Biobrane ® , Dressilk ® and PolyMem ® were compared with each other regarding objective and subjective healing parameters and cost efficiency. Methods 28 burn patients received surgical treatment with split-thickness skin grafting, while utilizing Biobrane ® , Dressilk ® and PolyMem ® as a single bound donor site wound dressing in all patients. Following a standardized case report form, we monitored several parameters such as pain, transparency of the dressing, active bleeding, exudation and inflammation by using the Verbal Rating Scale 1–10 through out. Results With regard to re-epithelialization, pain and acute bleeding all three dressings were equivalent. Dressilk ® and Biobrane ® presented clearly superior to PolyMem ® in both wound assessment and in the reduction of mild inflammation and exudation. High subjective satisfaction rates were reported with Dressilk ® and Biobrane ® dressings in regard to comfort and mobility. During the continuous monitoring period Biobrane ® outperformed Dressilk ® by providing higher wound transparency rates and offering a better level of wound control during the entire study period. Regarding their cost efficiency, PolyMem ® and Dressilk ® are clearly superior to Biobrane ® . Conclusion The "ideal" wound dressing maximizes patients' comfort while reducing pain and the risk of pulling off migrating epidermal cells from the wound surface. In addition reliable wound status evaluation (minimizing complications), an increase of treatment cost value efficacy, and reduced hospitalization rates should be provided. Dressilk ® and Biobrane ® were favored by patients and surgeons for providing an effective and safe healing environment, with overall low complication rates with respect to infection and exudation. Regarding cost-effectiveness PolyMem ® and Dressilk ® presented superior to Biobrane ® .

The bioactivity of neuropeptide Y (NPY) is either N-terminally modulated with respect to receptor selectivity by dipeptidyl peptidase 4 (DP4)-like enzymes or proteolytic degraded by neprilysin or meprins, thereby abrogating signal transduction. However, neither the subcellular nor the compartmental differentiation of these regulatory mechanisms is fully understood. Using mass spectrometry, selective inhibitors and histochemistry, studies across various cell types, body fluids, and tissues revealed that most frequently DP4-like enzymes, aminopeptidases P, secreted meprin-A (Mep-A), and cathepsin D (CTSD) rapidly hydrolyze NPY, depending on the cell type and tissue under study. Novel degradation of NPY by cathepsins B, D, L, G, S, and tissue kallikrein could also be identified. The expression of DP4, CTSD, and Mep-A at the median eminence indicates that the bioactivity of NPY is regulated by peptidases at the interphase between the periphery and the CNS. Detailed ex vivo studies on human sera and CSF samples recognized CTSD as the major NPY-cleaving enzyme in the CSF, whereas an additional C-terminal truncation by angiotensin-converting enzyme could be detected in serum. The latter finding hints to potential drug interaction between antidiabetic DP4 inhibitors and anti-hypertensive angiotensin-converting enzyme inhibitors, while it ablates suspected hypertensive side effects of only antidiabetic DP4-inhibitors application. The bioactivity of neuropeptide Y (NPY) is either N-terminally modulated with respect to receptor selectivity by dipeptidyl peptidase 4 (DP4)-like enzymes or proteolytic degraded by neprilysin or meprins, thereby abrogating signal transduction. However, neither the subcellular nor the compartmental differentiation of these regulatory mechanisms is fully understood. Using mass spectrometry, selective inhibitors and histochemistry, studies across various cell types, body fluids, and tissues revealed that most frequently DP4-like enzymes, aminopeptidases P, secreted meprin-A (Mep-A), and cathepsin D (CTSD) rapidly hydrolyze NPY, depending on the cell type and tissue under study. Novel degradation of NPY by cathepsins B, D, L, G, S, and tissue kallikrein could also be identified. The expression of DP4, CTSD, and Mep-A at the median eminence indicates that the bioactivity of NPY is regulated by peptidases at the interphase between the periphery and the CNS. Detailed ex vivo studies on human sera and CSF samples recognized CTSD as the major NPY-cleaving enzyme in the CSF, whereas an additional C-terminal truncation by angiotensin-converting enzyme could be detected in serum. The latter finding hints to potential drug interaction between antidiabetic DP4 inhibitors and anti-hypertensive angiotensin-converting enzyme inhibitors, while it ablates suspected hypertensive side effects of only antidiabetic DP4-inhibitors application.

Talk of mechanisms is ubiquitous in the natural sciences. Interdisciplinary fields such as biochemistry and pharmacy frequently discuss mechanisms with the assistance of diagrams. Such diagrams usually depict entities as structures or boxes and activities or interactions as arrows. While some of these arrows may indicate causal or componential relations, others may represent temporal or operational orders. Importantly, what kind of relation an arrow represents may not only vary with context but also be underdetermined by empirical data. In this manuscript, we investigate how an analysis of pharmacological mechanisms in terms of producing and underlying mechanisms—as discussed in the contemporary philosophy of science—may shed light on these issues. Specifically, we shall argue that while pharmacokinetic mechanisms usually describe causal chains of production, pharmacodynamics tends to focus on mechanisms of action underlying the in vivo effects of a drug. Considering the action of thyroid gland hormones in the human body as a case study, we further demonstrate that pharmacodynamic schemes tend to incorporate entities and interactions on multiple levels. Yet, traditional pharmacodynamic schemes are sketched “flat”, i.e., non-hierarchically. We suggest that transforming flat pharmacodynamic schemes into mechanistic multi-level representations may assist in disentangling the different kinds of mechanisms and relations depicted by arrows in flat schemes. The resulting Baumkuchen model provides a powerful and practical alternative to traditional flat schemes, as it explicates the relevant mechanisms and relations more clearly. On a more general note, our discussion demonstrates how pharmacology and related disciplines may benefit from applying concepts from the new mechanist philosophy to guide the interpretation of scientific diagrams.

To evaluate early and late responses in biological-naïve patients with rheumatoid arthritis (RA) initiating tocilizumab and early tocilizumab non-responders who switched to rituximab.In this open-label, non-randomised phase 3 study, RA patients with inadequate response to conventional synthetic DMARDs received tocilizumab 8 mg/kg intravenously at study begin and weeks 4, 8 and 12. After evaluation at week 16, early responders (Disease Activity Score based on 28 joints-erythrocyte sedimentation rate [DAS28-ESR]2.6) completed the study; partial responders (DAS28-ESR decrease1.2 or DAS28-ESR ≥2.6-≤3.2) were to continue tocilizumab through week 28; non-responders (DAS28-ESR decrease ≤1.2) switched to rituximab (1000 mg, weeks 16 and 18) with safety follow-up through week 66.Of 519 patients, 222 (42.8%) achieved early DAS28-ESR remission at week 16; 240 patients continued treatment, 213 (41.0%) received tocilizumab, and 27 (5.2%) switched to rituximab. At week 32 DAS28-ESR remission was achieved by 117/213 patients (54.9%) who continued tocilizumab and 4/27 patients (14.8%) who switched to rituximab; good EULAR response was achieved by 66.7% and 25.9% and CDAI remission by 19.2% and 14.8% of patients, respectively. Serious adverse events occurred through week 32 in 45/490 patients (9.2%) who received tocilizumab (serious infections, 2.7%) and through week 66 in 8/27 patients (29.6%) who switched to rituximab.Early response to tocilizumab was observed in 42.8% of patients. Half of early partial responders benefitted from continuing tocilizumab. Switching non-responders to rituximab seems feasible. No new safety signals were observed in patients treated with tocilizumab or switched to rituximab.

Background Ear and earlobe deformities after surgical rhytidectomy are common and can significantly diminish the aesthetic outcome. The main causes of ear/earlobe distortion are skin overresection, an imbalance between vertical/horizontal skin-lift vectors, and tractional distortions through superficial muscularaponeurotic system (SMAS) tension. Objectives To demonstrate a new method for earlobe suturing and ear fixation that would prevent aesthetics-related complications after facelift surgery. Methods A total of 105 primary SMAS facelift surgeries were performed between 2015 and 2016 by the first author. A combination technique consisting of a posterior earlobe rotation flap (PERF) and a concha-mastoid suspension suture (CMSS) was executed bilaterally within each facelift procedure (n = 210). A retrospective data analysis was conducted (preoperatively and one year postoperatively) using our hospital information system and a photometric data analysis to assess auricular displacement, earlobe distortion, and hypertrophic scarring. Results Pseudoptosis of the earlobe was noted in two cases, and auricular displacement was observed in four cases. Bilateral mild hypertrophic scarring was seen in one patient. The postoperative photometric analysis showed a natural ptosis grade I/II in all the patients, with a statistically significantly reduced postoperative earlobe size (P < 0.05). The total rate of aesthetics-related complications was 4% in our cohort (earlobe distortion with pseudoptosis: 1%; auricular displacement: 2%; hypertrophic scarring: 1%). Conclusions Our modification of the facial flap anchoring at the ear base in combination with a CMSS stabilizes the natural position of the ear and prevents distortion while allowing better control over the earlobe’s aesthetic shaping. This novel method reduces the incidence of ear/earlobe deformities and hypertrophic scarring at the ear base after rhytidectomy and, therefore, promises to be a valuable advancement. Level of Evidence: 4

Gesture and sign form an integrated communication system, as do gesture and speech. Communicative acts in both systems combine categorical linguistic (words or signs) with imagistic (gestures) components. Additionally, both sign and speech can employ modifying components that convey iconic information tied to a linguistic base morpheme. An accurate analysis of communicative acts must take this third category into account.

IntroductionIdiopathic nephrotic syndrome is the most common glomerular disease in childhood with an incidence of 1.8 cases per 100 000 children in Germany. The treatment of the first episode implies two aspects: induction of remission and sustainment of remission. The recent Kidney Disease Improving Global Outcomes, American Academy of Pediatrics and German guidelines for the initial treatment of the first episode of a nephrotic syndrome recommend a 12-week course of prednisone. Despite being effective, this treatment is associated with pronounced glucocorticoid-associated toxicity due to high-dose prednisone administration over a prolonged period of time. The aim of the INTENT study (Initial treatment of steroid-sensitive idiopathic nephrotic syndrom in children with mycophenolate mofetil versus prednisone: protocol for a randomised, controlled, multicentre trial) is to show that an alternative treatment regimen with mycophenolic acid is not inferior regarding sustainment of remission, but with lower toxicity compared with treatment with glucocorticoids only.Methods and designThe study is designed as an open, randomised, controlled, multicentre trial. 340 children with a first episode of steroid-sensitive nephrotic syndrome and who achieved remission by a standard prednisone regimen will be enrolled in the trial and randomised to one of two treatment arms. The standard care group will be treated with prednisone for a total of 12 weeks; in the experimental group the treatment is switched to mycophenolate mofetil, also for a total of 12 weeks in treatment duration. The primary endpoint is the occurrence of a treated relapse within 24 months after completion of initial treatment.Ethics and disseminationEthics approval for this trial was granted by the ethics committee of the Medical Faculty of the University of Heidelberg (AFmu-554/2014). The study results will be published in accordance with the Consolidated Standards of Reporting Trials statement and the Standard Protocol Items: Recommendations for Interventional Trials guidelines. Our findings will be submitted to major international paediatric nephrology and general paediatric conferences and submitted for publication in a peer-reviewed, open-access journal.Trial registration numberDRKS0006547; EudraCT2014-001991-76; Pre-result.Date of registration30 October 2014; 24 February 2017.

Background The length of stay (LOS) strongly influences anorexia nervosa (AN) inpatient weight outcomes. Hence, understanding the predictors of LOS is highly relevant. However, the existing evidence is inconsistent and to draw conclusions, additional evidence is required. Methods We conducted a prospective, multi-center study including adult female inpatients with AN. Using stepwise linear regression, the following demographic and clinical variables were examined as potential predictors for LOS: admission BMI, AN-subtype, age, age of onset, living situation, partnership status, education, previous hospitalization, self-rated depression, anxiety and somatic symptoms (PHQ-9, PHQ-15, GAD-7), self-rated therapy motivation (FEVER) and eating disorder psychopathology (EDI-2 subscale scores). Results The average LOS of the sample (n = 176) was 11.8 weeks (SD = 5.2). Longer LOS was associated with lower admission BMI (ß = −1.66; p