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Rationale & Objective: Adolescent and young adult kidney transplant recipients have a high risk of rejection related to suboptimal adherence. Multicomponent interventions improve adherence in controlled trials, but clinical implementation is lacking. We describe an initiative to reduce allograft rejection using evidence-based adherence promotion strategies., Study Design: Interrupted time series., Setting & Participants: Kidney transplant recipients cared for at Cincinnati Children's Hospital ≥ 1 year after transplant and taking ≥1 immunosuppressive medication(s) from 2014 through 2017., Quality Improvement Activities: The following interventions, collectively called MAPS (Medication Adherence Promotion System), were implemented over 14 months: (1) adherence promotion training for clinical staff, 2) electronic health record-supported adherence risk screening, (3) systematic assessment of medication adherence barriers, (4) designation of specific staff to address adherence barriers, (5) shared decision-making with the patients to overcome adherence barriers, (6) follow-up evaluation to assess progress, and (7) optional electronic medication monitoring., Outcomes: Primary Outcome: Late acute rejection. Process measures were conducted to assess barriers, identify barriers, and perform interventions. The secondary outcomes/balancing measures were de novo donor-specific antibodies (DSA), biopsy rate, and rejections per biopsy., Analytical Approach: Time series analysis using statistical process control evaluated patient-days between acute rejections as well as monthly rejections per 100 patient-months before and after implementation. To control for known rejection risk factors including changes in treatment and case mix, multivariable analyses were performed., Results: The monthly rejection rate fell from 1.61 rejections per 100 patient-months in the 26 months before implementation to 0.88 rejections per 100 patient-months in the 22 months after implementation. In the multivariable analysis, MAPS was associated with a 50% reduction in rejection incidence (incidence rate ratio, 0.50 [95% CI, 0.27-0.91]; P = 0.02). DSA and time since transplant (per each additional year) were also associated with rejection incidence (incidence rate ratio, 2.27 [P = 0.02] and 0.87 [P = 0.02], respectively)., Limitations: Single-center study, and potential confounding by unmeasured variables., Conclusions: Clinical implementation of evidence-based adherence-promotion strategies was associated with a 50% reduction in acute rejection incidence over 2 years., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare no funding or conflicts of interest.

Introduction: Control beliefs can protect against age-related declines in functioning. It is unclear whether neighborhood characteristics shape how much control people perceive over their life. This article studies associations of neighborhood characteristics with control beliefs of residents of a diverse metropolitan area (Berlin, Germany)., Methods: We combine self-report data about perceptions of control obtained from participants in the Berlin Aging Study II (N = 507, 60-87 years, 51% women) with multisource geo-referenced indicators of neighborhood characteristics using linear regression models., Results: Findings indicate that objective neighborhood characteristics (i.e., unemployment rate) are indeed tied to perceptions of control, in particular, how much control participants feel others have over their lives. Including neighborhood characteristics in part doubled the amount of explained variance compared with a reference model covarying for demographic characteristics only (from R2 = 0.017 to R2 = 0.030 for internal control beliefs; R2 = 0.056 to R2 = 0.102 for external control beliefs in chance; R2 = 0.006 to R2 = 0.030 for external control beliefs in powerful others)., Discussion/conclusion: Findings highlight the importance of access to neighborhood resources for control beliefs across old age and can inform interventions to build up neighborhood characteristics which might be especially helpful in residential areas with high unemployment., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background: The oncogene epidermal growth factor receptor variant III (EGFRvIII) is expressed in approximately one-third of all glioblastomas (GBMs). So far it is not clear if EGFRvIII expression induces replication stress in GBM cells, which might serve as a therapeutical target., Methods: Isogenetic EGFRvIII- and EGFRvIII+ cell lines with endogenous EGFRvIII expression were used. Markers of oncogenic and replication stress such as γH2AX, RPA, 53BP1, ATR, and CHK1 were analyzed using western blot, immunofluorescence, and flow cytometry. The DNA fiber assay was performed to analyze replication, transcription was measured by incorporation of EU, and genomic instability was investigated by micronuclei and CGH-Array analysis. Immunohistochemistry staining was used to detect replication stress markers and R-loops in human GBM samples., Results: EGFRvIII+ cells exhibit an activated replication stress response, increased spontaneous DNA damage, elevated levels of single-stranded DNA, and reduced DNA replication velocity, which are all indicative characteristics of replication stress. Furthermore, we show here that EGFRvIII expression is linked to increased genomic instability. EGFRvIII-expressing cells display elevated RNA synthesis and R-loop formation, which could also be confirmed in EGFRvIII-positive GBM patient samples. Targeting replication stress by irinotecan resulted in increased sensitivity of EGFRvIII+ cells., Conclusion: This study demonstrates that EGFRvIII expression is associated with increased replication stress, R-loop accumulation, and genomic instability. This might contribute to intratumoral heterogeneity but may also be exploited for individualized therapy approaches., (© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background : A high prevalence of poor job satisfaction and high chronic stress is documented for general practitioners (GPs) and non-physician practice staff from various countries. The reasons are multifactorial and include deficits in leadership, communication and workflows. This publicly funded study evaluates the effectiveness of the newly developed participatory, interdisciplinary, and multimodal IMPROVE job intervention on improving job satisfaction among GPs and practice personnel. Here, we report the baseline characteristics of the participating GPs and practice assistants, focusing on job satisfaction and perceived chronic stress. Methods : The IMPROVE job study was performed as a cluster-randomised, controlled trial (cRCT) with German GP practices in the North Rhine Region. The IMPROVE job intervention comprised two leadership workshops (one for practice leaders only; a second for leaders and practice assistants), a toolbox with supplemental printed and online material, and a nine-month implementation phase supported by IMPROVE job facilitators. The intervention addressed issues of leadership, communication, and work processes. During study nurse visits, participants completed questionnaires at baseline and after nine months follow up. The primary outcome was the change in job satisfaction as measured by the respective scale of the validated German version of the Copenhagen Psychosocial Questionnaire (German COPSOQ, version 2018). Perceived chronic stress was measured using the Trier Inventory of Chronic Stress (TICS- SSCS). Results : Recruitment of 60 practices was successful: 21 were solo, 39 were group practices. At baseline, n = 84 practice owners, n = 28 employed physicians and n = 254 practice assistants were included. The mean age of all participants was 44.4 (SD = 12.8). At baseline, the job satisfaction score in the total sample was 74.19 of 100 (±14.45) and the perceived chronic stress score was 19.04 of 48 (±8.78). Practice assistants had a significantly lower job satisfaction than practice owners ( p < 0.05) and employed physicians ( p < 0.05). In the regression analysis, perceived chronic stress was negatively associated with job satisfaction (b= -0.606, SE b = 0.082, p < 0.001, ICC = 0.10). Discussion : The degree of job satisfaction was similar to those in other medical professionals published in studies, while perceived chronic stress was markedly higher compared to the general German population. These findings confirm the need for interventions to improve psychological wellbeing in GP practice personnel.

Background: Successful renal transplantation requires complex medication regimens that rely on strict adherence to be effective. Variability in immunosuppression exposure, specifically tacrolimus, is associated with poor allograft outcomes. Wide intra-patient variability of tacrolimus trough concentrations (Vtac) is likely, in part, attributable to regimen complexity and poor medication adherence. Once-daily tacrolimus formulations create opportunity to simplify therapeutic regimens, and this study aims to evaluate their impact on Vtac and ultimately transplant outcomes., Methods: This retrospective cohort study investigated stable (AYA) renal transplant recipients converted from (IR-Tac) to (ER-Tac). Subjects served as their own controls. Vtac was assessed by measuring the (SD) of serial tacrolimus trough concentrations prior to and at four time points post-conversion to ER-Tac over 24-month follow-up. Secondary outcome measures included graft function, infection rates, and effect on modifiable treatment-related factors., Results: Twenty-eight AYA subjects were converted from IR-Tac to ER-Tac. Vtac significantly improved following conversion and was sustained for 24 months (Vtac 0 2.32 vs. Vtac 24 1.11, p .017). Renal function remained stable, and (BPAR) rates were modest (14%). Mean pill burden was reduced by 15%, and 42.9% of subjects achieved a once-daily medication regimen., Conclusions: Conversion from IR-Tac to ER-Tac in this AYA population significantly improved Vtac with sustained effect over 2 years. This effect is likely attributable in part to simplification of the medication regimen and presumably improved medication adherence. Such conversion does not appear to compromise graft function for at least 2 years post-conversion., (© 2021 Wiley Periodicals LLC.)

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Immunogenicity assays are required to evaluate anti-drug antibody (ADA) responses that can be generated against biotherapeutic modalities. Regulatory guidelines focus on clinical requirements, yet it has become apparent that industry has applied these clinical recommendations for immunogenicity assessment to nonclinical studies in varying degrees. ADAs are an anticipated outcome of dosing a humanized or fully human biotherapeutic into an animal. However, a nonclinical ADA response is rarely predictive of the immunogenic potential in humans. The addendum to ICH S6 recommends that immunogenicity should be explicitly examined where there is: evidence of altered pharmacodynamic activity; unexpected changes in exposure in the absence of a pharmacodynamic marker or evidence of immuno-mediated reactions. The European Bioanalytical Forum has extensively discussed and reached a consensus on a minimal strategic approach of when and what to include for nonclinical immunogenicity assessments. Additionally, this paper recommends a strategy for ADA assay validation and sample analysis for those cases when it is considered necessary to include an immunogenicity assessment in nonclinical toxicology studies.

The SARS-CoV-2 coronavirus has spread rapidly across Germany. Infections are likely to be under-recorded in the notification data from local health authorities on laboratory-confirmed cases since SARS-CoV-2 infections can proceed with few symptoms and then often remain undetected. Seroepidemiological studies allow the estimation of the proportion in the population that has been infected with SARS-CoV-2 (seroprevalence) as well as the extent of undetected infections. The 'CORONA-MONITORING bundesweit' study (RKI-SOEP study) collects biospecimens and interview data in a nationwide population sample drawn from the German Socio-Economic Panel (SOEP). Participants are sent materials to self-collect a dry blood sample of capillary blood from their finger and a swab sample from their mouth and nose, as well as a questionnaire. The samples returned are tested for SARS-CoV-2 IgG antibodies and SARS-CoV-2 RNA to identify past or present infections. The methods applied enable the identification of SARS-CoV-2 infections, including those that previously went undetected. In addition, by linking the data collected with available SOEP data, the study has the potential to investigate social and health-related differences in infection status. Thus, the study contributes to an improved understanding of the extent of the epidemic in Germany, as well as identification of target groups for infection protection., Competing Interests: Conflicts of interest The authors declared no conflicts of interest., (© Robert Koch Institute. All rights reserved unless explicitly granted.)

Dyslipidemia after kidney transplantation is a common complication that has historically been underappreciated, especially in pediatric recipients. It is also a major modifiable risk factor for cardiovascular disease, a top cause of morbidity and mortality of transplant patients. While most knowledge about post-transplant dyslipidemia has been generated in adults, recommendations and treatment strategies also exist for children and are presented in this review. Awareness of these applicable guidelines and approaches is required, but not sufficient, for the reliable management of dyslipidemia in our patients, and additional needs and opportunities for comprehensive care in this area (e.g., quality improvement) are outlined.

Purpose: To describe the outcomes of allograft ocular surface stem cell transplantation (OSST) and the complication profile of systemic immunosuppression (SI) in pediatric patients with limbal stem cell deficiency., Methods: This was a retrospective interventional case series from a single tertiary referral institution of 20 eyes from 13 patients who 1) underwent allograft OSST surgery, 2) were 18 years or less at time of OSST, and 3) received SI with 4) a minimum of 12-months follow-up. The main outcome measures were ocular surface stability, visual acuity, and SI adverse events., Results: The mean age of patients was 15.1 ± 3.2 years (range 9-18 years). The mean follow-up was 5.6 ± 5.0 years after OSST. At the last follow-up, 15 eyes (75%) had a stable ocular surface, 1 eye (5%) developed partial failure, and 4 eyes (20%) developed total surface failure. Preoperative mean logarithm of the minimum angle of resolution visual acuity 1.5 improved to 1.1 at the last follow-up (P = 0.1); when 4 eyes of 3 nonadherent patients were excluded, the results were more pronounced and statistically significant (1.5 improved to 1.0, P = 0.002). SI was tolerated well by all patients with minimal adverse events., Conclusions: OSST provides a stable ocular surface and is a successful treatment option for pediatric patients with limbal stem cell deficiency. SI is well-tolerated with a minimal complication profile.

The ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp) and ABCG2 are multidrug transporters that confer drug resistance to numerous anti-cancer therapeutics in cell culture. These findings initially created great excitement in the medical oncology community, as inhibitors of these transporters held the promise of overcoming clinical multidrug resistance in cancer patients. However, clinical trials of P-gp and ABCG2 inhibitors in combination with cancer chemotherapeutics have not been successful due, in part, to flawed clinical trial designs resulting from an incomplete molecular understanding of the multifactorial basis of multidrug resistance (MDR) in the cancers examined. The field was also stymied by the lack of high-resolution structural information for P-gp and ABCG2 for use in the rational structure-based drug design of inhibitors. Recent advances in structural biology have led to numerous structures of both ABCG2 and P-gp that elucidated more clearly the mechanism of transport and the polyspecific nature of their substrate and inhibitor binding sites. These data should prove useful helpful for developing even more potent and specific inhibitors of both transporters. As such, although possible pharmacokinetic interactions would need to be evaluated, these inhibitors may show greater effectiveness in overcoming ABC-dependent multidrug resistance in combination with chemotherapeutics in carefully selected subsets of cancers. Another perhaps even more compelling use of these inhibitors may be in reversibly inhibiting endogenously expressed P-gp and ABCG2, which serve a protective role at various blood-tissue barriers. Inhibition of these transporters at sanctuary sites such as the brain and gut could lead to increased penetration by chemotherapeutics used to treat brain cancers or other brain disorders and increased oral bioavailability of these agents, respectively., Competing Interests: Conflicts of interest All authors declared that there are no conflicts of interest.

Trichodysplasia spinulosa is a rare disorder caused by the ubiquitous trichodysplasia spinulosa-associated polyomavirus (TSPyV) and characterized clinically by predominately centrofacial, but often generalized, folliculocentric papules with protuberant keratinaceous spines. Although seroprevalence reaches up to 70% in adult populations, TSPyV causes clinical manifestations in a small percentage of patients who are immunosuppressed. Diagnosis can be made using typical clinical and histologic features, SV40T antibody immunostaining, and PCR of various tissues including the keratinaceous spine, skin, serum, urine, and CSF. Various topical and systemic medications have demonstrated variable success. Decreasing or discontinuing immunosuppression has also been shown to improve or alleviate clinical manifestations., (© 2020 Wiley Periodicals LLC.)

The ATR kinase plays a key role in the DNA damage response by activating essential signaling pathways of DNA damage repair, especially in response to replication stress. Because DNA damage and replication stress are major sources of genomic instability, selective ATR inhibition has been recognized as a promising new approach in cancer therapy. We now report the identification and preclinical evaluation of the novel, clinical ATR inhibitor BAY 1895344. Starting from quinoline 2 with weak ATR inhibitory activity, lead optimization efforts focusing on potency, selectivity, and oral bioavailability led to the discovery of the potent, highly selective, orally available ATR inhibitor BAY 1895344, which exhibited strong monotherapy efficacy in cancer xenograft models that carry certain DNA damage repair deficiencies. Moreover, combination treatment of BAY 1895344 with certain DNA damage inducing chemotherapy resulted in synergistic antitumor activity. BAY 1895344 is currently under clinical investigation in patients with advanced solid tumors and lymphomas (NCT03188965).

Background and Purpose: Detailed insight into the composition of thrombi retrieved from patients with ischemic stroke by mechanical thrombectomy might improve pathophysiologic understanding and therapy. Thus, this study searched for links between histologic thrombus composition and stroke subtypes and mechanical thrombectomy results., Materials and Methods: Thrombi from 85 patients who had undergone mechanical thrombectomy for acute ischemic stroke between December 2016 and March 2018 were studied retrospectively. Thrombi were examined histologically. Preinterventional imaging features, stroke subtypes, and interventional parameters were re-analyzed. Statistical analysis was performed with the Kruskal-Wallis test, Mann-Whitney U test, or Spearman correlation as appropriate., Results: Cardioembolic thrombi had a higher percentage of macrophages and a tendency toward more platelets than thrombi of large-artery atherosclerotic stenosis ( P = .021 and .003) or the embolic stroke of undetermined source ( P = .037 and .099) subtype. Thrombi prone to fragmentation required the combined use of contact aspiration and stent retrieval ( P = .021) and were associated with an increased number of retrieving maneuvers ( P = .001), longer procedural times ( P = .001), and a higher lymphocyte content ( P = .035)., Conclusions: We interpreted the higher macrophage and platelet content in cardioembolic thrombi compared with large-artery atherosclerotic stenosis or embolic stroke of undetermined source thrombi as an indication that the latter type might be derived from an atherosclerotic plaque rather than from an undetermined cardiac source. The extent of thrombus fragmentation was associated with a more challenging mechanical thrombectomy and a higher lymphocyte content of the thrombi. Thus, thrombus fragmentation not only might be caused by the recanalization procedure but also might be a feature of a lymphocyte-rich, difficult-to-retrieve subgroup of thrombi., (© 2020 by American Journal of Neuroradiology.)

The oncogene epidermal growth factor receptor variant III (EGFRvIII) is frequently expressed in glioblastomas (GBM) but its impact on therapy response is still under controversial debate. Here we wanted to test if EGFRvIII influences the sensitivity towards the alkylating agent temozolomide (TMZ). Therefore, we retrospectively analyzed the survival of 336 GBM patients, demonstrating that under standard treatment, which includes TMZ, EGFRvIII expression is associated with prolonged survival, but only in patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylated tumors. Using isogenic GBM cell lines with endogenous EGFRvIII expression we could demonstrate that EGFRvIII increases TMZ sensitivity and results in enhanced numbers of DNA double-strand breaks and a pronounced S/G2-phase arrest after TMZ treatment. We observed a higher expression of DNA mismatch repair (MMR) proteins in EGFRvIII+ cells and patient tumor samples, which was most pronounced for MSH2 and MSH6. EGFRvIII-specific knockdown reduced MMR protein expression thereby increasing TMZ resistance. Subsequent functional kinome profiling revealed an increased activation of p38- and ERK1/2-dependent signaling in EGFRvIII expressing cells, which regulates MMR protein expression downstream of EGFRvIII. In summary, our results demonstrate that the oncoprotein EGFRvIII sensitizes a fraction of GBM to current standard of care treatment through the upregulation of DNA MMR.

In this article, organisers of the annual conference of the Comparative and International Education Society (CIES), held during March and April 2020, share their story of moving the planned on-site conference to a virtual space, as necessitated by the COVID-19 pandemic. Their analysis of the vCIES (the name given to the virtual conference) process not only provides an example of a disruption to the status quo of the institution of conferencing as a result of a global pandemic, but also extends it by addressing the multiplying concerns, urgent considerations and actions needed within academic communities for more equal and accessible conferencing in the unfolding climate catastrophe. The authors begin by discussing the challenge of academic conferencing in the age of COVID-19 and climate crisis. They highlight how their decolonial political stance (which critiques accepting Western knowledge and Western culture as the norm) and their climate-conscious approach informed their preparation of a virtual conference pilot already intended as an experimental extension to this year's on-site event. They suggest the development of this pilot provided the necessary platform for transforming the vCIES into an effective and engaging virtual experience for participants. The vCIES process, including considerations concerning its structure and format and the necessary technology, is detailed in the subsequent sections. In the final part of their article, the authors briefly identify and discuss some of the opportunities, challenges and implications emerging from their vCIES experiences. Ultimately, they suggest that in a time of instability, insecurity and uncertainty, there need to be alternatives to large on-site conferences which require excessive and extensive academic mobility. The vCIES was a step in that direction as an accessible, environmentally responsive, more equal, and intergenerational and multispecies event that welcomed families, children and pets, while opening the space for new interdisciplinary encounters., (© UNESCO Institute for Lifelong Learning and Springer Nature B.V. 2020.)

Rationale and Objectives: Mechanical thrombectomy is common practice in proximal anterior vessel occlusion. However, it remains unclear whether peripheral artery occlusions should be treated as well. This retrospective study aimed to prove the effectiveness of endovascular recanalization treatment for the M2 segment by comparison of intracranial internal carotid artery (ICA), M1 segment, and M2 segment thrombectomy., Materials and Methods: All patients who received endovascular treatment for distal ICA, M1, or M2 segment occlusions between January 2010 and July 2017 at our center were re-analyzed with respect to reperfusion success, interventional and clinical parameters. Statistical analysis was performed by Mann Whitney test, Chi square test, and Spearman correlation analysis., Results: A total of 261 patients (median age, 72 years), 100 with ICA, 137 with M1, and 24 with M2 segment occlusion, were included. Duration of endovascular treatment was significantly longer in ICA occlusions (median, 83 minutes, p < 0.001) compared to M1 (56 minutes) or M2 segment occlusions (49 minutes). Recanalization and reperfusion success and rate of endovascular complications did not differ between occlusion sites (AOL, p = 0.071; mTICI, p = 0.540; complications, p = 0.064). No significant difference in revascularization success was found between the different thrombectomy devices (direct thrombus aspiration, stent retrieving, or a sequential combined approach; p = 0.112). Successful M2 recanalization (mTICI 2b-3) correlated significantly with stronger posttherapeutic NIHSS reduction (r = 0.691, p < 0.001)., Conclusion: We found endovascular treatment of M2 segment occlusions as safe and successful as endovascular therapy of the ICA or M1 segment, with stronger posttherapeutic NIHSS reduction after successful compared to insufficient M2 recanalization., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Prevalence and implications of anti-HLA class I and class II antibodies are beginning to be better characterized in pediatric kidney transplant recipients. dnDSA formation is predictive of AMR and downstream diminished graft function and survival. However, risk factors for the development of dnDSA are not well defined in this patient population. After introducing DSA surveillance into our pediatric kidney transplant program, we are reporting the prevalence of class I and class II DSA in 67 otherwise stable recipients. Secondary end-points included risk factors for DSA development and assessment of graft function. Significantly, lower median daily MMF doses were observed in patients with DSAs compared to patients without DSAs (371 vs 617 mg/m 2 /d, respectively; P = 0.035). Class II DSA formation was more common, with a prevalence of 17.9%, as compared to 10.4% for class I DSA. Estimated glomerular filtration rate was also decreased in patients with positive DSA vs those with negative titers (71, SD 25 vs 78, SD 29 mL/min/1.73 m 2 , respectively; P = 0.034). We conclude that reduced-dose MMF is associated with dnDSA and DSA is associated with diminished graft function in stable pediatric kidney transplant recipients., (© 2019 Wiley Periodicals, Inc.)

Aim: To quantify the frequency of bacterial contamination of the injected contrast agent/saline solution by an automated contrast injection system, and to evaluate whether usage of a novel tube system can reduce it. Methods: For bacterial contamination quantification two identical automated piston pump MRI contrast injectors were used in combination with a standard tube system. 3-5 ml of the contrast agent/saline solution was collected from the system prior to its connection to the patients' venous cannula in 104 consecutive patients. To test, whether a novel tube system reduces contamination, a tube system with shielded screw connections was used with the same contrast injectors and contrast agent/saline samples were collected in further 101 patients. Specimens were microbiologically analyzed. Frequencies of contamination were compared using Fisher exact test. Results: With the standard tube system, bacterial contamination was observed in 5.8% (6 out of 104 specimens). With the novel tube system, contamination was observed in 2.0% (2 out of 101 specimens, p=0.280). Staphylococcus epidermidis was the most common germ (5 cases) followed by Micrococcus luteus (2 cases) and Oligella ureolytica (1 case). Conclusion: Bacterial contaminations of MRI contrast injectors occurred in a non-negligible frequency especially with S. epidermidis . A trend towards reduced bacterial contamination was seen when a novel tube system with shielded screw connections was used., Competing Interests: The authors declare that they have no competing interests.

During the last two decades, it has been well established that a short-term exposure to ozone (O 3 ) elicits an oxidative stress response in human and mouse skin, which leads to aberrant transcriptional expression of genes consistent with increased skin aging. Whether a long-term exposure to ambient O 3 is associated with any skin aging traits, has remained unclear. We addressed this question in two elderly German cohorts: the SALIA study (806 women aged 66-79 years), and the BASE-II study (1207 men and women aged 60-84 years). Five-year mean residential exposure to O 3 was modeled as the number of days with maximum daily 8-h mean O 3 concentrations ≥120 μg/m 3 per year in the wider neighborhood (5-digit postcode) of a participant's residence. Extrinsic (environmentally induced) skin aging traits - coarse wrinkles and pigment spots (lentigines) on the face - were assessed by means of SCINEXA™, a validated visual score previously shown to be well suited to measure extrinsic facial skin aging in cohort studies. We observed positive associations of O 3 exceedances with coarse wrinkles in the face, but not with pigment spots. These associations were present in each cohort as well as in the combined sample of both cohorts. They were independent of chronic ultraviolet radiation exposure as the most obvious confounder, and also of co-pollutants such as particulate matter and nitrogen dioxide. Thus, long-term exposure to elevated concentrations of tropospheric O 3 appears to contribute to skin aging., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To assess composite health outcomes in pediatric and young adult kidney transplant recipients following kidney transplantation., Study Design: We conducted a cross-sectional study of all recipients at our center who had a 1-, 3-, 5-, and/or 10-year transplant anniversary visit between October 2008 and February 2015. The kidney transplant recipients were assessed at each time point according to an outcome measure consisting of 15 pass/fail criteria in 5 domains: allograft health, rejection and immunology, infection, cardiovascular health, and growth., Results: We analyzed 148 patients at 231 transplantation anniversary visit time points; 52 of 82 (63%) patients assessed at 1 year had an ideal outcome, meeting at least 13 of the 15 criteria. This decreased to 37% at year 3, 40% at year 5, and 26% at year 10 (P < .01). The most common failures across all time points occurred in the domains of growth (43%-52% passing) and cardiovascular health (33%-51% passing). Allograft health declined significantly, decreasing from 74% at year 1 to 33% at year 10 (P < .01). The percentage of patients with graft failure increased from 2.4% at 1 year to 39.5% at 10 years (P < .01), and patient deaths increased from 0 to 11% (P < .01) in the same time frame., Conclusions: Ideal outcomes for pediatric kidney transplant recipients decrease over time with growth, cardiovascular health, and allograft health as the primary failure modes. Understanding the composite health of young recipients will allow primary care providers and nephrologists alike to evaluate the overall health of kidney transplant recipients and focus clinical care on the most common sequelae., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To determine if there is an association between mortality and admission chloride levels and/or increases in the chloride level in critically ill children., Methods: We performed a retrospective cohort study of all patients admitted to the paediatric intensive care unit (PICU) from January 2014 to December 2015. Patients were excluded for the following reasons: (1) age < 90 days or > 18 years, (2) admission to the cardiac intensive care unit, (3) no laboratory values upon admission to the PICU, (4) history of end-stage renal disease, (5) a disorder of chloride transport, and (6) admission for diabetic ketoacidosis. The patients were stratified on the basis of admission chloride levels (hypochloraemia, < 96 mEq/L; normochloraemia, 96-109 mEq/L; and hyperchloraemia, ≥ 110 mEq/L) and dichotomised on the basis of an increase in chloride in the first day (< 5 mEq/L, ≥ 5 mEq/L). Our primary outcome was in-hospital mortality., Results: A total of 1935 patients [55% female, median age 6.3 years IQR (1.9-13.4)] were included. The overall mortality was 4% (n = 71) and day 2 AKI occurred in 17% (n = 333. Hypochloraemia, hyperchloraemia, and an increase in serum chloride ≥ 5 mEq/L occurred in 2%, 21%, and 12%, respectively. After adjusting for confounders, increase in chloride ≥ 5 mEq/L was associated with a 2.3 (95% CI 1.03-5.21) greater odds of mortality., Conclusions: An increase in serum chloride level in the first day of admission is common and an independent risk factor for mortality in critically ill children. Further studies are warranted to identify how chloride disturbances contribute to mortality risk in critically ill children.

Purpose: Computer-aided diagnosis (CAD) appears promising in early ischemic change detection computed tomography (CT). This study aimed to compare the performance of two new CAD systems (Frontier ASPECTS Prototype and Brainomix) with two experienced readers in selected patients with suspected acute ischemic stroke., Methods: Retrospectively, non-contrast brain CTs of 150 patients suspected for acute middle cerebral artery ischemia were analyzed with respect to ASPECTS first separately, than in consensus by two senior radiologists, and by use of Frontier and Brainomix. Besides the fully automatic Frontier and Brainomix readings (Frontier&#95;1, Brainomix&#95;1), readings adjusted for the affected brain side (known by CT angiography or clinical presentation, Frontier&#95;2, Brainomix&#95;2) were assessed. Statistical analysis was performed by intraclass correlation and Bland-Altman statistics., Results: The score-based ASPECTS readings of Brainomix&#95;1, Brainomix&#95;2, both radiologists, and the expert consensus reading correlated highly (r = 0.714 to 0.841; always p < 0.001), whereas Frontier&#95;1 and Frontier&#95;2 correlated only lowly or moderately with both radiologists, the expert consensus reading, and Brainomix (r = 0.471 to 0.680; always p < 0.001). Bland-Altman analysis revealed lower mean ASPECT difference and standard deviation of difference for Brainomix&#95;2 (mean difference = -0.2; SD = 1.15) compared to Frontier&#95;2 (mean difference = 1.2; SD = 1.76). Correlation of region-based ASPECTS reading with the expert consensus reading was moderate for Brainomix&#95;2 (r = 0.534), but only low for Frontier&#95;2 (r = 0283; always p < 0.001)., Conclusion: We found high agreement in ASPECTS rating between both radiologists, expert consensus reading, and Brainomix, but only low to moderate agreement to Frontier.

Objectives: (1) To describe the accessibility of general practitioners (GPs) by the German population; (2) to determine factors on individual and area level, such as settlement structure and area deprivation, which are associated with the walking distance to a GP; and (3) to identify factors that may cause differences in the utilisation of any doctors., Design: Cross-sectional study using individual survey data from the representative German Socio-Economic Panel (SOEP) linked with area deprivation data from the German Index of Multiple Deprivation for 2010 (GIMD 2010) and official data for settlement structure (urban/rural areas) at district level. Logistic regression models were estimated to determine the relationship of individual and area factors with the distance to a GP. Negative binomial regressions were used to analyse the association with utilisation., Setting: Germany., Population: n=20 601 respondents from the SOEP survey data 2009., Primary Outcome Measure: Walking distance to a GP., Secondary Outcome Measure: Doctor visits., Results: Nearly 70% of the sample lives within a 20 min walk to a GP. People living in the most deprived areas have a 1.4-fold (95% CI 1.3 to 1.6) increased probability of a greater walking distance compared with the least deprived quintile, even after controlling for settlement structure and individual factors. In rural districts, people have a 3.1-fold (95% CI 2.8 to 3.4) higher probability of a greater walking distance compared with those in cities. Both area deprivation and rurality have a negative relationship with the utilisation of physicians, whereas the distance to a GP is not associated with the utilisation of physicians., Conclusion: Walking distance to a GP depends on individual and area factors. In Germany, area deprivation is negatively correlated with the accessibility of GPs while controlling for settlement structure and individual factors. Both area factors are negatively associated with the utilisation of doctors. This knowledge could be used for future GP requirement plans., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: This study examined the feasibility of aortic valve planimetry at 7 T ultrahigh field MRI in intraindividual comparison to 3 T and 1.5 T MRI., Material and Methods: Aortic valves of eleven healthy volunteers (mean age, 26.4 years) were examined on a 7 T, 3 T, and 1.5 T MR system using FLASH and TrueFISP sequences. Two experienced radiologists evaluated overall image quality, the presence of artefacts, tissue contrast ratios, identifiability, and image details of the aortic valve opening area (AVOA). Furthermore, AVOA was quantified twice by reader 1 and once by reader 2. Correlation analysis between artefact severity and employed magnetic field strength was performed by modified Fisher's exac t -test. Paired t -test was used to analyse for AVOA differences, and Bland-Altman plots were used to analyse AVOA intra-rater and inter-rater variability., Results: Aortic valve imaging at 7 T, 3 T, and 1.5 T with using FLASH was less hampered by artefacts than TrueFISP imaging at 3 T and 1.5 T. Tissue contrast and image details were rated best at 7 T. AVOA was measured slightly smaller at 7 T compared to 3 T (TrueFISP, p-value = 0.057; FLASH, p-value = 0.016) and 1.5 T (TrueFISP, p-value = 0.029; FLASH, p-value = 0.018). Intra-rater and inter-rater variability of AVOA tended to be slightly smaller at 7 T than at 3 T and 1.5 T., Conclusion: Aortic valve planimetry at 7 T ultrahigh field MRI is technically feasible and in healthy volunteers offers an improved tissue contrast and a slightly better reproducibility than MR planimetry at 1.5 T and 3 T.

Background: Nephrotic syndrome can be caused by a subgroup of mitochondrial diseases classified as primary coenzyme Q 10 (CoQ 10 ) deficiency. Pathogenic COQ2 variants are a cause of primary CoQ 10 deficiency and present with phenotypes ranging from isolated nephrotic syndrome to fatal multisystem disease., Case-Diagnosis/treatment: We report three pediatric patients with COQ2 variants presenting with nephrotic syndrome. Two of these patients had normal leukocyte CoQ 10 levels prior to treatment. Pathologic findings varied from mesangial sclerosis to focal segmental glomerulosclerosis, with all patients having abnormal appearing mitochondria on kidney biopsy. In two of the three patients treated with CoQ 10 supplementation, the nephrotic syndrome resolved; and at follow-up, both have normal renal function and stable proteinuria., Conclusions: COQ2 nephropathy should be suspected in patients presenting with nephrotic syndrome, although less common than disease due to mutations in NPHS1, NPHS2, and WT1. The index of suspicion should remain high, and we suggest that providers consider genetic evaluation even in patients with normal leukocyte CoQ 10 levels, as levels may be within normal range even with significant clinical disease. Early molecular diagnosis and specific treatment are essential in the management of this severe yet treatable condition.

Purpose: A prerequisite for cardiac MR (CMR) imaging is adequate synchronization of image acquisition with the cardiac cycle. Electrocardiogram triggering may be hampered by electromagnetic interferences at high field strength. The purpose of this work is to evaluate the feasibility of Doppler ultrasound triggering for CMR image synchronization at 7T ultra-high-field MRI., Methods: A custom-built Doppler ultrasound (DUS) trigger device was developed. Magnetic resonance compatibility was evaluated using E- and H-field probes and flip angle maps prior to the study. Cardiac MR was performed at 7T in 13 healthy subjects using DUS and pulse oximetry for triggering. For validation of the trigger signal, the electrocardiogram, pulse, and DUS signals were compared outside of the MR room. Breath-hold cine fast low-angle-shot sequences were acquired in short-axis and four-chamber view. Image quality was assessed by two senior radiologists and by measurement of endocardial blurring., Results: The maximal change in E- and H-field distributions with and without transducer was 5%. No interferences were observed between DUS and MRI in the B 1 maps and during CMR imaging. Validation of the DUS trigger signal resulted in a high correlation to the electrocardiographic signal of r = 0.99. Analysis of image and trigger quality revealed no significant differences., Conclusion: Doppler ultrasound was applied as a new trigger method in CMR at 7T. The transmission line and transducer were locally approved as 7T MR conditional, and were successfully tested for image synchronization at 7T. In the future, this method needs to be evaluated in a larger patient population. Magn Reson Med 80:239-247, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Objective: Besides cardiac sarcoidosis, FDG-PET is rarely used in the diagnosis of myocardial inflammation, while cardiac MRI (CMR) is the actual imaging reference for the workup of myocarditis. Using integrated PET/MRI in patients with suspected myocarditis, we prospectively compared FDG-PET to CMR and the feasibility of integrated FDG-PET/MRI in myocarditis., Methods: A total of 65 consecutive patients with suspected myocarditis were prospectively assessed using integrated cardiac FDG-PET/MRI. Studies comprised T2-weighted imaging, late gadolinium enhancement (LGE), and simultaneous PET acquisition. Physiological glucose uptake in the myocardium was suppressed using dietary preparation., Results: FDG-PET/MRI was successful in 55 of 65 enrolled patients: two patients were excluded due to claustrophobia and eight patients due to failed inhibition of myocardial glucose uptake. Compared with CMR (LGE and/or T2), sensitivity and specificity of PET was 74% and 97%. Overall spatial agreement between PET and CMR was κ = 0.73. Spatial agreement between PET and T2 (κ = 0.75) was higher than agreement between PET and LGE (κ = 0.64) as well as between LGE and T2 (κ = 0.56)., Conclusion: In patients with suspected myocarditis, FDG-PET is in good agreement with CMR findings.

Background: The optimal fluid management in critically ill children is currently under investigation with several studies suggesting that hyperchloremia, chloride load, and the use of chloride-rich fluids contribute to worse outcomes., Methods: This is a single-center retrospective cohort study of Pediatric Intensive Care Unit patients from 2008 to 2016 requiring continuous renal replacement therapy (CRRT). Patients were excluded if they had end-stage renal disease, a disorder of chloride transport, or concurrent provision of extracorporeal membrane oxygenation therapy., Results: Patients (n = 66) were dichotomized into two groups (peak chloride (Cl) ≥ 110 mmol/L vs. peak Cl < 110 mmol/L prior to CRRT initiation). Hyperchloremia was present in 39 (59%) children. Baseline characteristics were similar between groups. Fluid overload at CRRT initiation was more common in patients with hyperchloremia (11.5% IQR 3.8-22.4) compared to those without (5.5% IQR 0.9-13.9) (p = 0.04). Mortality was significantly higher in patients with hyperchloremia (n = 26, 67%) compared to those without (n = 8, 29%) (p = 0.006). Patients with hyperchloremia had 10.9 times greater odds of death compared to those without hyperchloremia, after adjusting for percent fluid overload, PRISM III score, time to initiation of CRRT, height, and weight (95% CI 2.4 to 49.5, p = 0.002)., Conclusions: Hyperchloremia is common among critically ill children prior to CRRT initiation. In this population, hyperchloremia is independently associated with mortality. Further studies are needed to determine the impact of hyperchloremia on all critically ill children and the impact of chloride load on outcomes.

Background: An early posttransplant biomarker/surrogate marker for kidney allograft loss has the potential to guide targeted interventions. Previously published findings, including results from the Clinical Trials in Organ Transplantation (CTOT)-01 study, showed that elevated urinary chemokine CXCL9 levels and elevated frequencies of donor-reactive interferon gamma (IFNγ)-producing T cells by enzyme-linked immunosorbent spot (ELISPOT) assay associated with acute cellular rejection within the first year and with lower 1-year posttransplant estimated glomerular filtration rate (eGFR). How well these biomarkers correlate with late outcomes, including graft loss, is unclear., Methods: In CTOT-17, we obtained 5-year outcomes in the CTOT-01 cohort and correlated them with (a) biomarker results and (b) changes in eGFR (Chronic Kidney Disease Epidemiology Collaboration formula) over the initial 2 years posttransplant using univariable analysis and multivariable logistic regression., Results: Graft loss occurred in 14 (7.6%) of 184 subjects 2 to 5 years posttransplant. Neither IFNγ ELISPOTs nor urinary CXCL9 were informative. In contrast, a 40% or greater decline in eGFR from 6 months to 2 years posttransplant independently correlated with 13-fold odds of 5-year graft loss (adjusted odds ratio, 13.1; 95% confidence interval, 3.0-56.6), a result that was validated in the independent Genomics of Chronic Allograft Rejection cohort (n = 165; adjusted odds ratio, 11.2)., Conclusions: We conclude that although pretransplant and early posttransplant ELISPOT and chemokine measurements associate with outcomes within 2 years posttransplant, changes in eGFR between 3 or 6 months and 24 months are better surrogates for 5-year outcomes, including graft loss.

Non-adherence remains a significant problem among pediatric (and adult) renal transplant recipients. Non-adherence among solid organ transplant recipients results in US$15-100 million annual costs. Estimates of non-adherence range from 30 to 70% among pediatric patients. Research demonstrates that a 10% decrement in adherence is associated with 8% higher hazard of graft failure and mortality. Focus has begun to shift from patient factors that impact adherence to the contributing healthcare and systems factors. The purpose of this review is to describe problems within the systems implicated in non-adherence and potential solutions that may be related to positive adherence outcomes. Systems issues include insurance and legal regulations, provider and care team barriers to optimal care, and difficulties with transitioning to adult care. Potential solutions include recognition of how systems can work together to improve patient outcomes through improvements in insurance programs, a multi-disciplinary care team approach, evidence-based medical management, pharmacy-based applications and interventions to simplify medication regimens, improved transition protocols, and telehealth/technology-based multi-component interventions. However, there remains a significant lack of reliability in the application of these potential solutions to systems issues that impact patient adherence. Future efforts should accordingly focus on these efforts, likely by leveraging quality improvement and related principles, and on the investigation of the efficacy of these interventions to improve adherence and graft outcomes.

The Open Source Registry for Rare Diseases (OSSE) provides a concept and a software for the management of registries for patients with rare diseases. A disease is defined as rare if less than 5 out of 10,000 people are affected. Up to date, approximately 6,000 rare diseases are catalogued. Networking and data exchange for research purposes remains challenging due to the paucity of interoperability and due to the fact that small data stocks are stored locally. The so called "Findable, Accessible, Interoperable, Reusable" (FAIR) Data Principles have been developed to improve research in the field of rare diseases. Subsequently, the OSSE architecture was adapted to implement the FAIR Data Principles. Therefore, the so-called FAIR Data Point was integrated into OSSE to provide a description of metadata in a FAIR manner. OSSE relies on the existing metadata repository (MDR), which is used in to define data elements in the system. This is an important step towards unified documentation across multiple registries. The integration and use of new procedures to improve interoperability plays an important role in the context of registries for rare diseases.

Purpose: Standardized computer-aided tumor response assessment is common in clinical trials. In contrast, unstructured free text reporting (UFTR) is common in daily routine. Therefore, this study aimed to discern and quantify differences between UFTR and computer-aided standardized tumor response evaluation based on RECIST 1.1 criteria (RECIST), serving as gold standard, in clinical workflow., Methods: One-hundred consecutive patients with cancer eligible for RECIST 1.1 evaluation, who received five follow-up CTs of the trunk, were retrospectively included. All UFTRs were assigned to RECIST response categories [complete response, partial response (PR), stable disease (SD), progressive disease (PD)]. All CTs were re-evaluated using dedicated software (mint lesion™) applying RECIST 1.1. The accordance in tumor response ratings was analyzed using Cohen's kappa., Results: At the first follow-up, 47 cases were rated differently with an SD underrepresentation and a PR and PD overrepresentation in UFTR. In the subsequent follow-ups, categorical differences were seen in 38, 44, 37, and 44%. Accordance between UFTR and RECIST was fair to moderate (Cohen's kappa: 0.356, 0.477, 0.390, 0.475, 0.376; always p < 0.001). Differences were mainly caused by the rating of even small tumor burden changes as PD or PR in UFTR or by comparison to the most recent prior CT scan in UFTR instead of comparison to nadir or baseline., Conclusions: Significant differences in tumor response ratings were detected comparing UFTR and computer-aided standardized evaluation based on RECIST 1.1. Thus, standardized reporting should be implemented in daily routine workflow.

MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P = .038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This paper presents diagnostic criteria for Menière's disease jointly formulated by the Classification Committee of the Bárány Society, The Japan Society for Equilibrium Research, the European Academy of Otology and Neurotology (EAONO), the Equilibrium Committee of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and the Korean Balance Society. The classification includes two categories: definite Menière's disease and probable Menière's disease. The diagnosis of definite Menière's disease is based on clinical criteria and requires the observation of an episodic vertigo syndrome associated with low- to medium-frequency sensorineural hearing loss and fluctuating aural symptoms (hearing, tinnitus and/or fullness) in the affected ear. Duration of vertigo episodes is limited to a period between 20 min and 12 h. Probable Menière's disease is a broader concept defined by episodic vestibular symptoms (vertigo or dizziness) associated with fluctuating aural symptoms occurring in a period from 20 min to 24 h.

Background: Corticosteroids used as immunosuppressants to prevent acute rejection (AR) and graft loss (GL) following kidney transplantation are associated with serious cardiovascular and other adverse events. Evidence from short-term randomized controlled trials suggests that many patients on a tacrolimus-based immunosuppressant regimen can withdraw from steroids without increased AR or GL risk., Objectives: To measure the long-term tradeoff between GL and adverse events for a heterogeneous-risk population and determine the optimal timing of steroid withdrawal., Methods: A discrete event simulation was developed including, as events, AR, GL, myocardial infarction (MI), stroke, cytomegalovirus, and new onset diabetes mellitus (NODM), among others. Data from the United States Renal Data System were used to estimate event-specific parametric regressions, which accounted for steroid-sparing regimen (avoidance, early 7-d withdrawal, 6-mo withdrawal, 12-mo withdrawal, and maintenance) as well as patients' demographics, immunologic risks, and comorbidities. Regression-equation results were used to derive individual time-to-event Weibull distributions, used, in turn, to simulate the course of patients over 20 y., Results: Patients on steroid avoidance or an early-withdrawal regimen were more likely to experience AR (45.9% to 55.0% v. 33.6%, P < 0.05) and GL (51.5% to 68.8% v. 37.8%, P < 0.05) compared to patients on steroid maintenance. Patients in 6-mo and 12-mo steroid withdrawal groups were less likely to experience MI (11.1% v. 13.3%, P < 0.05), NODM (30.7% to 34.4% v. 37.7%, P < 0.05), and cardiac death (29.9% to 30.5% v. 32.4%, P < 0.05), compared to steroid maintenance., Conclusions: Strategies of 6- and 12-mo steroid withdrawal post-kidney transplantation are expected to reduce the rates of adverse cardiovascular events and other outcomes with no worsening of AR or GL rates compared with steroid maintenance.

Enriched environments elicit brain plasticity in animals. In humans it is unclear which environment is enriching. Living in a city has been associated with increased amygdala activity in a stress paradigm, and being brought up in a city with increased pregenual anterior cingulate cortex (pACC) activity. We set out to identify geographical characteristics that constitute an enriched environment affecting the human brain. We used structural equation modelling on 341 older adults to establish three latent brain factors (amygdala, pACC and dorsolateral prefrontal cortex (DLPFC)) to test the effects of forest, urban green, water and wasteland around the home address. Our results reveal a significant positive association between the coverage of forest and amygdala integrity. We conclude that forests may have salutogenic effects on the integrity of the amygdala. Since cross-sectional data does not allow causal inference it could also be that individuals with high structural integrity choose to live closer to forest.

Background: Nephrotic syndrome represents a condition in pediatric nephrology typified by a relapsing and remitting course, proteinuria and the presence of edema. The PROMIS measures have previously been studied and validated in cross-sectional studies of children with nephrotic syndrome. This study was designed to longitudinally validate the PROMIS measures in pediatric nephrotic syndrome., Methods: One hundred twenty seven children with nephrotic syndrome between the ages of 8 and 17 years participated in this prospective cohort study. Patients completed a baseline assessment while their nephrotic syndrome was active, a follow-up assessment at the time of their first complete proteinuria remission or study month 3 if no remission occurred, and a final assessment at study month 12. Participants completed six PROMIS measures (Mobility, Fatigue, Pain Interference, Depressive Symptoms, Anxiety, and Peer Relationships), the PedsQL version 4.0, and two global assessment of change items., Results: Disease status was classified at each assessment: nephrotic syndrome active in 100% at baseline, 33% at month 3, and 46% at month 12. The PROMIS domains of Mobility, Fatigue, Pain Interference, Depressive Symptoms, and Anxiety each showed a significant overall improvement over time (p < 0.001). When the PROMIS measures were compared to the patients' global assessment of change, the domains of Mobility, Fatigue, Pain Interference, and Anxiety consistently changed in an expected fashion. With the exception of Pain Interference, change in PROMIS domain scores did not correlate with changes in disease activity. PROMIS domain scores were moderately correlated with analogous PedsQL domain scores., Conclusion: This study demonstrates that the PROMIS Mobility, Fatigue, Pain Interference, and Anxiety domains are sensitive to self-reported changes in disease and overall health status over time in children with nephrotic syndrome. The lack of significant anchoring to clinically defined nephrotic syndrome disease active and remission status may highlight an opportunity to improve the measurement of HRQOL in children with nephrotic syndrome through the development of a nephrotic syndrome disease-specific HRQOL measure.

Purpose  Adrenal incidentaloma (AI) and adrenal masses in cases of subclinical Cushing's syndrome (SCS) initially require follow-up imaging. In this study we used endoscopic ultrasound (EUS) as a method for high-resolution imaging. The aim was to evaluate the growth rate of AI and SCS by EUS. Materials and Methods  This retrospective analysis included 93 out of 229 patients with AI or SCS who were investigated longitudinally by EUS in our university hospital between 1997 and 2013. The longitudinal follow-up required at least two investigations by EUS and evaluation of endocrine function. Plasma renin, serum aldosterone, 24 h urinary catecholamines and 2 mg dexamethasone suppression test were performed. EUS was performed at baseline and during follow-up. Each time, the maximum diameter was measured. Three groups were defined: non-functioning adenomas (NFA), non-functioning nodular hyperplasias (NFH) and SCS. Results  86 patients had non-functioning masses [NFM] (59 NFA, 48 NFH) and 7 patients had SCS (10 masses). At baseline the mean diameter was 19.4 (± 9.3) mm (NFM) and 19.6 (± 9.2) mm (SCS). The mean follow-up period was 31.6 ± 28.7 months. The estimated mean growth rates per year were low: They were 0.35 mm/yr [NFA], 0.02 mm/yr [NFH] and 0.53 mm/yr [SCS]. Furthermore, there was no malignant progression of any mass. Conclusion  The growth rate as determined by EUS was low for all tumor entities observed in this study. There was no difference in tumor growth between the groups., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background Cardiac magnetic resonance imaging (MRI) relies on correct ECG-gating, which is hindered in arrhythmia. Purpose To examine whether a prototype free-breathing real-time cine sequence using SPARSE-SENSE (SPARSE) improves left ventricular quantification in atrial fibrillation. Material and Methods On a 1.5T MR system left ventricular short-axis stacks were acquired of the SPARSE sequence and of a "reference" steady-state free precession (SSFP) sequence with arrhythmia rejection in 20 patients with atrial fibrillation. Two radiologists independently rated arrhythmia-caused artifact severity in both sequences using a 4-point scale. Coefficients of variation of myocardial signal intensity for both sequences were acquired. Volumetry was performed twice by one reader and once by another reader. Correlation between artifact severity and employed sequence was analyzed by modified Fisher's exact test. Coefficients of variation and volumetric data were compared by paired t-test and intraclass correlation. Results Median arrhythmia-caused artifact severity was 2 in both readers for SSFP and 0 (reader 1)/1 (reader 2) for SPARSE, being significantly lower in SPARSE ( P < 0.001). Mean coefficient of variance was significantly smaller in SPARSE (0.11 ± 0.04) compared to SSFP (0.22 ± 0.13, P = 0.003), which was interpreted as a hint for fewer artifacts in SPARSE. Only a small difference of 9 ± 15 mL was seen for end-systolic volume ( P = 0.019) between sequences, otherwise no significant difference was detected (end-diastolic volume, P = 0.200; stroke volume, P = 0.554; ejection fraction, P = 0.136; myocardial mass, P = 0.353). Intraclass correlation between sequences was good to excellent (range, 0.80-0.97). Conclusion Real-time MRI with SPARSE data sampling is promising in atrial fibrillation because it reduces arrhythmia-caused artifacts.

Since first performed in 1954, kidney transplantation has evolved as the preferred long-term treatment of children with end stage renal disease (ESRD). The etiology of chronic kidney disease (CKD) and ESRD in children is broad and can be quite complicated, necessitating a multidisciplinary team to adequately care for these patients and their myriad needs. Precise surgical techniques and modern protocols for immunosuppression provide excellent long-term patient and graft survival. This article reviews the many etiologies of renal failure in the pediatric population focusing on those most commonly leading to the need for kidney transplantation. The processes of evaluation, kidney transplantation, short-term and long-term complications, as well as long-term outcomes are also reviewed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Open-ended questions have routinely been included in large-scale survey and panel studies, yet there is some perplexity about how to actually incorporate the answers to such questions into quantitative social science research. Tools developed recently in the domain of natural language processing offer a wide range of options for the automated analysis of such textual data, but their implementation has lagged behind. In this study, we demonstrate straightforward procedures that can be applied to process and analyze textual data for the purposes of quantitative social science research. Using more than 35,000 textual answers to the question "What else are you worried about?" from participants of the German Socio-economic Panel Study (SOEP), we (1) analyzed characteristics of respondents that determined whether they answered the open-ended question, (2) used the textual data to detect relevant topics that were reported by the respondents, and (3) linked the features of the respondents to the worries they reported in their textual data. The potential uses as well as the limitations of the automated analysis of textual data are discussed.

Both lifespan psychology and life course sociology highlight that contextual factors influence individual functioning and development. In the current study, we operationalize context as county-level care services in inpatient and outpatient facilities (e.g., number of care facilities, privacy in facilities) and investigate how the care context shapes well-being in the last years of life. To do so, we combine 29 waves of individual-level longitudinal data on life satisfaction from now deceased participants in the nationwide German Socio-Economic Panel Study ( N  = 4557; age at death: M  = 73.35, SD = 14.20; 47% women) with county-level data from the Federal Statistical Office. Results from three-level growth models revealed that having more inpatient care facilities, more employees per resident, and more staff in administration are each uniquely associated with higher late-life well-being, independent of key individual (age at death, gender, education, disability) and county (affluence, demographic composition) characteristics. Number of employees in physical care, residential comfort, and flexibility and care indicators in outpatient institutions were not found to be associated with levels or change in well-being. We take our results to provide empirical evidence that some contextual factors shape well-being in the last years of life and discuss possible routes how local care services might alleviate terminal decline.

Introduction: Radioembolization for the treatment of hepatocellular carcinoma (HCC) induces liver volume changes referred to as "atrophy-hypertrophy complex". The aim of this study was to investigate lobar liver volume changes after unilateral radioembolization and to search for factors associated with hypertrophy of the untreated lobe., Materials and Methods: Seventy-five patients were retrospectively evaluated. Inclusion criteria were: (1) right-lobar radioembolization for unresectable unilateral HCC, (2) available liver computed tomography scans before, 1, 3, and at least 6 months after radioembolization. Baseline patient characteristics included clinical features, laboratory results, spleen volume, and liver computed tomography. Absolute and relative (referred to the whole liver volume) liver lobe volumes (LLV) as well as relative LLV (rLLV) change per month were evaluated and compared., Results: Absolute and relative contralateral LLV continuously increased after radioembolization (p<0.001). Mean relative contralateral LLV increased from 36±11.6% before radioembolization to 50±15.3% 6 months after radioembolization. Median contralateral rLLV increase/month (within first 6 months) was 2.5%. Contralateral rLLV increase/month was significantly lower in patients with ascites (p = 0.017) or platelet count <100/nl (p = 0.009). An inverse correlation of contralateral rLVV increase/month with spleen volume (p = 0.017), patient age (p = 0.024), Child Pugh score (p = 0.001), and tumor burden (p = 0.001) was found., Conclusions: Significant contralateral hypertrophy and ipsilateral atrophy were common after unilateral radioembolization. Small spleen volume, low patient age, low Child Pugh score, absence of ascites, platelet count ≥100/nl, and low tumor burden were associated with increased contralateral hypertrophy, indicating that younger patients with compensated cirrhosis might benefit most from radioembolization in a "bridge-to-resection" setting.