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Objectives This study aims to better characterize potential responders of Y-90-radioembolization at baseline through analysis of clinical variables and contrast enhanced (CE) MRI tumor volumetry in order to adjust therapeutic regimens early on and to improve treatment outcomes. Methods Fifty-eight HCC patients who underwent Y-90-radioembolization at our center between 10/2008 and 02/2017 were retrospectively included. Pre- and post-treatment target lesion volumes were measured as total tumor volume (TTV) and enhancing tumor volume (ETV). Survival analysis was performed with Cox regression models to evaluate 65% ETV reduction as surrogate endpoint for treatment efficacy. Univariable and multivariable logistic regression analyses were used to evaluate the combination of baseline clinical variables and tumor volumetry as predictors of ≥ 65% ETV reduction. Results Mean patients’ age was 66 (SD 8.7) years, and 12 were female (21%). Sixty-seven percent of patients suffered from liver cirrhosis. Median survival was 11 months. A threshold of ≥ 65% in ETV reduction allowed for a significant (p = 0.04) separation of the survival curves with a median survival of 11 months in non-responders and 17 months in responders. Administered activity per tumor volume did predict neither survival nor ETV reduction. A baseline ETV/TTV ratio greater than 50% was the most important predictor of arterial devascularization (odds ratio 6.3) in a statistically significant (p = 0.001) multivariable logistic regression model. The effect size was strong with a Cohen’s f of 0.89. Conclusion We present a novel approach to identify promising candidates for Y-90 radioembolization at pre-treatment baseline MRI using tumor volumetry and clinical baseline variables. Key Points • A decrease of 65% enhancing tumor volume (ETV) on follow-up imaging 2–3 months after Y-90 radioembolization of HCC enables the early prediction of significantly improved median overall survival (11 months vs. 17 months, p = 0.04). • Said decrease in vascularization is predictable at baseline: an ETV greater than 50% is the most important variable in a multivariable logistic regression model that predicts responders at a high level of significance (p = 0.001) with an area under the curve of 87%.

Expansions of donor pools have a controversial impact on healthcare expenditures. The aim of this study was to investigate the emerging costs of expanded criteria donor (ECD) kidney transplantations (KT) and to identify independent risk factors for increased transplant-related costs. We present a retrospective explorative analysis of hospital costs and reimbursements of KTs performed between 2012 and 2016 in a German university hospital. A total of 174 KTs were examined, including 92 (52.9%) ECD organ transplantations. The ECD group comprised 43 (24.7%) 'old-for-old' transplantations. Median healthcare costs were 19 570€ (IQR 18 735-27 405€) in the standard criteria donor (SCD) group versus 25 478€ (IQR 19 957-29 634€) in the ECD group (+30%; P = 0.076). 'Old-for-old' transplantations showed the highest healthcare expenditures [26 702€ (19 570-33 940€)]. Irrespective of the allocation group, transplant-related costs increased significantly in obese (+6221€; P = 0.009) and elderly recipients (+6717€; P = 0.019), in warm ischaemia time exceeding 30 min (+3212€; P = 0.009) and in kidneys with DGF or surgical complications (+8976€ and +10 624€; both P < 0.001). Transplantation of ECD organs is associated with incremental costs, especially in elderly and obese recipients. A critical patient selection, treatment of obesity before KT and keeping warm ischaemia times short seem to be crucial, in order to achieve a cost-effective KT regardless of the allocation group.

ObjectiveWe aimed to investigate the proportion of young patients not returning to work (NRTW) at 1 year after ischemic stroke (IS) and during follow-up, and clinical factors associated with NRTW.MethodsPatients from the Helsinki Young Stroke Registry with an IS occurring in the years 1994–2007, who were at paid employment within 1 year before IS, and with NIH Stroke Scale score ≤15 points at hospital discharge, were included. Data on periods of payment came from the Finnish Centre for Pensions, and death data from Statistics Finland. Multivariate logistic regression analyses assessed factors associated with NRTW 1 year after IS, and lasagna plots visualized the proportion of patients returning to work over time.ResultsWe included a total of 769 patients, of whom 289 (37.6%) were not working at 1 year, 323 (42.0%) at 2 years, and 361 (46.9%) at 5 years from IS. When adjusted for age, sex, socioeconomic status, and NIH Stroke Scale score at admission, factors associated with NRTW at 1 year after IS were large anterior strokes, strokes caused by large artery atherosclerosis, high-risk sources of cardioembolism, and rare causes other than dissection compared with undetermined cause, moderate to severe aphasia vs no aphasia, mild and moderate to severe limb paresis vs no paresis, and moderate to severe visual field deficit vs no deficit.ConclusionsNRTW is a frequent adverse outcome after IS in young adults with mild to moderate IS. Clinical variables available during acute hospitalization may allow prediction of NRTW.

Promoting patient and occupational safety are two key challenges for hospitals. When aiming to improve these two outcomes synergistically, psychosocial working conditions, leadership by hospital management and supervisors, and perceptions of patient and occupational safety climate have to be considered. Recent studies have shown that these key topics are interrelated and form a critical foundation for promoting patient and occupational safety in hospitals. So far, these topics have mainly been studied independently from each other. The present study investigated hospital staffs' perceptions of four different topics: (1) psychosocial working conditions, (2) leadership, (3) patient safety climate, and (4) occupational safety climate. We present results from a survey in two German university hospitals aiming to detect differences between nurses and physicians.We performed a cross-sectional study using a standardized paper-based questionnaire. The survey was conducted with nurses and physicians to assess the four topics. The instruments mainly consisted of scales of the German version of the COPSOQ (Copenhagen Psychosocial Questionnaire), one scale of the Copenhagen Burnout Inventory (CBI), scales to assess leadership and transformational leadership, scales to assess patient safety climate using the Hospital Survey on Patient Safety Culture (HSPSC), and analogous items to assess occupational safety climate.A total of 995 completed questionnaires out of 2512 distributed questionnaires were returned anonymously. The overall response rate was 39.6%. The sample consisted of 381 physicians and 567 nurses. We found various differences with regard to the four topics. In most of the COPSOQ and the HSPSC-scales, physicians rated psychosocial working conditions and patient safety climate more positively than nurses. With regard to occupational safety, nurses indicated higher occupational risks than physicians.The WorkSafeMed study combined the assessment of the four topics psychosocial working conditions, leadership, patient safety climate, and occupational safety climate in hospitals. Looking at the four topics provides an overview of where improvements in hospitals may be needed for nurses and physicians. Based on these results, improvements in working conditions, patient safety climate, and occupational safety climate are required for health care professionals in German university hospitals - especially for nurses.

Background: Stereotactic radiosurgery (SRS) is an effective treatment for trigeminal neuralgia (TN). Nevertheless, a proportion of patients will experience recurrence and treatment-related sensory disturbances. In order to evaluate the predictors of efficacy and safety of image-guided non-isocentric radiosurgery, we analyzed the impact of trigeminal nerve volume and the nerve dose/volume relationship, together with relevant clinical characteristics. Methods: Two-hundred and ninety-six procedures were performed on 262 patients at three centers. In 17 patients the TN was secondary to multiple sclerosis (MS). Trigeminal pain and sensory disturbances were classified according to the Barrow Neurological Institute (BNI) scale. Pain-free-intervals were investigated using Kaplan Meier analyses. Univariate and multivariate Cox regression analyses were performed to identify predictors. Results: The median follow-up period was 38 months, median maximal dose 72.4 Gy, median target nerve volume 25 mm(3), and median prescription dose 60 Gy. Pain control rate (BNI I-III) at 6, 12, 24, 36, 48, and 60 months were 96.8, 90.9, 84.2, 81.4, 74.2, and 71.2%, respectively. Overall, 18% of patients developed sensory disturbances. Patients with volume ≥ 30 mm(3) were more likely to maintain pain relief (p = 0.031), and low integral dose (< 1.4 mJ) tended to be associated with more pain recurrence than intermediate (1.4-2.7 mJ) or high integral dose (> 2.7 mJ; low vs. intermediate: log-rank test, χ(2) = 5.02, p = 0.019; low vs. high: log-rank test, χ(2) = 6.026, p = 0.014). MS, integral dose, and mean dose were the factors associated with pain recurrence, while re-irradiation and MS were predictors for sensory disturbance in the multivariate analysis. Conclusions: The dose to nerve volume ratio is predictive of pain recurrence in TN, and re-irradiation has a major impact on the development of sensory disturbances after non-isocentric SRS. Interestingly, the integral dose may differ significantly in treatments using apparently similar dose and volume constraints.

This study examined differences in personality, psychological distress, and stress coping in inflammatory bowel disease (IBD) depending on type of disease and disease activity. We compared patients suffering from Crohn's disease (CD) and ulcerative colitis (UC) with controls. While the literature is replete with distinctive features of the pathogenesis of IBD, the specific differences in psychological impairments are not well studied. In this German national multicenter study, participants were recruited from 32 centers. Two hundred ninety-seven questionnaires were included, delivering vast information on disease status and psychological well-being based on validated instruments with a total of 285 variables. CD patients were more affected by psychological impairments than patients suffering from UC or controls. Importantly, patients with active CD scored higher in neuroticism (p 0.01), psychological distress (p 0.001) and maladaptive stress coping (escape, p = 0.03; rumination, p 0.03), but less need for social support (p = 0.001) than controls. In contrast, patients suffering from active UC showed psychological distress (p 0.04) and maladaptive coping (avoidance, p 0.03; escape, p = 0.01). Patients in remission seemed to be less affected. In particular, patients with UC in remission were not inflicted by psychological impairments. The group of CD patients in remission however, showed insecurity (p 0.01) and paranoid ideation (p = 0.04). We identified specific aspects of psychological impairment in IBD depending on disease and disease activity. Our results underscore the need for psychological support and treatment particularly in active CD. Diese Studie untersuchte Unterschiede in der Persönlichkeit, psychische Belastung und Stressbewältigung bei chronisch-entzündlichen Darmerkrankungen (CED) in Abhängigkeit von der Art der Erkrankung und der Krankheitsaktivität. Wir verglichen Patienten mit Morbus Crohn (CD) und Colitis ulcerosa (UC) mit Kontrollgruppen. Während die Literatur zu charakteristischen Merkmalen der Pathogenese von IBD zahlreich ist, sind die spezifischen Unterschiede in den psychischen Beeinträchtigungen nicht ausreichend untersucht. In dieser deutschen nationalen Multicenterstudie wurden Teilnehmer aus 32 Zentren rekrutiert. Es wurden 297 Fragebögen mit umfassenden Informationen über den Krankheitsstatus und das psychische Wohlbefinden auf der Grundlage validierter psychosozialer Instrumente mit insgesamt 285 Items evaluiert. CD-Patienten waren stärker von psychischen Beeinträchtigungen betroffen als Patienten mit UC oder Kontrollen. Wichtig ist, dass Patienten mit aktiver CD in den Bereichen Neurotizismus (p 0,01), psychische Belastung (p 0,001) und maladaptive Stressbewältigung (p 0,03) höhere Werte, aber weniger Bedarf für soziale Unterstützung (p = 0,001) als Kontrollen aufwiesen. Im Gegensatz dazu zeigten Patienten, die an aktiver UC litten, psychische Belastung (p 0,04) und maladaptive Coping (Vermeidung, p 0,03; Flucht, p = 0,01). Patienten in Remission schienen weniger betroffen zu sein. Die Gruppe der CD-Patienten in Remission zeigte jedoch Unsicherheit (p 0,01). Wir identifizierten spezifische Aspekte der psychischen Beeinträchtigung bei IBD abhängig von Krankheit und Krankheitsaktivität. Unsere Ergebnisse untermauern den Bedarf an psychologischer Unterstützung und Behandlung, insbesondere bei aktiver CD.

The underlying genetic mechanisms and early pathological events of children with primary cardiomyopathy (CMP) are insufficiently characterized. In this study, we aimed to characterize the mutational spectrum of primary CMP in a large cohort of patients ���18 years referred to a tertiary center. Eighty unrelated index patients with pediatric primary CMP underwent genetic testing with a panel-based next-generation sequencing approach of 89 genes. At least one pathogenic or probably pathogenic variant was identified in 30/80 (38%) index patients. In all CMP subgroups, patients carried most frequently variants of interest in sarcomere genes suggesting them as a major contributor in pediatric primary CMP. In MYH7, MYBPC3, and TNNI3, we identified 18 pathogenic/probably pathogenic variants (MYH7 n = 7, MYBPC3 n = 6, TNNI3 n = 5, including one homozygous (TNNI3 c.24+2T>A) truncating variant. Protein and transcript level analysis on heart biopsies from individuals with homozygous mutation of TNNI3 revealed that the TNNI3 protein is absent and associated with upregulation of the fetal isoform TNNI1. The present study further supports the clinical importance of sarcomeric mutation-not only in adult-but also in pediatric primary CMP. TNNI3 is the third most important disease gene in this cohort and complete loss of TNNI3 leads to severe pediatric CMP.

Background Studies from multiple countries have shown that acute kidney injury (AKI) in hospitalized patients is associated with mortality and morbidity. There are no reliable data at present on the incidence and mortality of AKI episodes among hospitalized patients in Germany. The utility of administrative codings of AKI for the identification of AKI episodes is also unclear. Methods In an exploratory approach, we retrospectively analyzed all episodes of AKI over a period of 3.5 years (2014-2017) on the basis of routinely obtained serum creatinine measurements in 103 161 patients whose creatinine had been measured at least twice and who had been in the hospital for at least two days. We used the "Kidney Disease: Improving Global Outcomes" (KDIGO) criteria for AKI. In parallel, we assessed the administrative coding of discharge diagnoses of the same patients with codes from the International Classification of Diseases (ICD-10-GM). Results Among 185 760 hospitalizations, stage 1 AKI occurred in 25 417 cases (13.7%), stage 2 in 8503 cases (4.6%), and stage 3 in 5881 cases (3.1%). AKI cases were associated with length of hospital stay, renal morbidity, and overall mortality, and this association was stage-dependent. The in-hospital mortality was 5.1% for patients with stage 1 AKI, 13.7% for patients with stage 2 AKI, and 24.8% for patients with stage 3 AKI. An administrative coding for acute kidney injury (N17) was present in only 28.8% (11 481) of the AKI cases that were identified by creatinine criteria. Like the AKI cases overall, those that were identified by creatinine criteria but were not coded as AKI had significantly higher mortality, and this association was stage-dependent. Conclusion AKI episodes are common among hospitalized patients and are associated with considerable morbidity and mortality, yet they are inadequately documented and probably often escape the attention of the treating physicians.

OBJECTIVEMoyamoya vasculopathy (MMV) is a steno-occlusive cerebrovascular disease that can be treated by a surgical revascularization. All the revascularization techniques influence the blood supply of the scalp, with a risk for wound healing disorders. The authors’ aim was to analyze the wound healing process in the patients who underwent a direct or combined bypass surgery with a focus on different skin incisions.METHODSThe authors retrospectively identified all the patients with MMV who were treated surgically in their institution. Subsequently, they analyzed demographic data, clinical symptoms, surgical treatment, and detailed history of complications. Based on the evolution of their surgical techniques and the revascularization strategy to be used, the authors applied the following skin incisions: linear incision, curved incision, incomplete Y incision, and complete Y incision. Group comparisons regarding wound healing disorders were performed with significance testing using Fisher’s exact test.RESULTSThe authors identified 172 patients with MMV (61.6% moyamoya disease, 7% unilateral moyamoya disease, 29.7% moyamoya syndrome, and 1.7% unilateral moyamoya syndrome), of whom 124 underwent bilateral operations. One-quarter of the patients were juveniles. A total of 236 hemispheres were included in the analysis, of which 27.9% were treated by a combined procedure with encephalomyosynangiosis. Overall, 5.1% major and 1.7% minor wound complications occurred. The overall wound complication rate was lower in direct revascularization compared to combined revascularization (3% vs 15.2%). The lowest incidence of wound healing disorders was found in the linear incision group for the parietal superficial temporal artery branch (1.6%), followed by the incomplete Y incision group for the frontal branch of the superficial temporal artery (3.8%) in the direct bypass group. In the combined revascularization cohort, major or minor wound disorders appeared in 14.3% and 4.8%, respectively, in the complete Y incision group and in 4.2% (for both major and minor) in the curved incision group. The complete Y incision caused significantly more wound healing disorders compared to the remaining incision types (17.1% vs 3.1%, p = 0.007).CONCLUSIONSWound healing disorders are one of the major complications of revascularization surgery. Their incidence depends on the revascularization strategy and skin incision applied, with a complete Y incision giving the worst results.

Anthracycline cardiomyopathy is of concern in children treated for acute myeloid leukaemia (AML), but there are few data on the incidence and natural history of cardiotoxicity after AML treatment in the United Kingdom, where regimens have included high anthracycline exposure.Prevalence and predictors of cardiotoxicity were retrospectively reviewed in 124 children treated on the MRC AML 10 and AML 12 trials in a single, large centre from November 1987 to September 2004. Subclinical cardiotoxicity was defined as a shortening fraction of less than 28% and clinical cardiomyopathy as evidence of heart failure, and both were classified as late cardiotoxicity 1 year after completing first line therapy.Cumulative survival was 61% at 10 years. The prevalence of early and late cardiotoxicity was 13.7% (95%-CI: 8.2-22.0%) and 17.4% (95%-CI: 10.9-26.8%), respectively. Early cardiotoxicity was a strong predictor (OR = 9.18; 95%-CI: 2.10-40.11; P0.005) and children who received salvage therapy following relapse showed a trend towards increased late cardiotoxicity (OR = 3.53; 95%-CI: 0.86-14.48; P0.08). Subclinical cardiotoxicity resolved spontaneously in all but one case, but clinical cardiomyopathy always required continuing therapy. Two children died of cardiomyopathy and six remained on medical therapy.Anthracycline cardiotoxicity remains a major concern for survivors of childhood AML and correlates with early cardiotoxicity and treatment intensity. Long-term follow-up is required to fully determine the outcome for children with subclinical cardiotoxicity.