Risk Stratification and Clinical Characteristics of Patients with Late Recurrence of Melanoma (>10 Years)

Background: Most patients with high-risk melanomas develop metastasis within the first few years after diagnosis. However, late recurrence of melanoma is seen in patients that metastasize more than 10 years after the primary diagnosis; a metastasis after 15 years is considered an ultra-late recurrence. It is critical to better understand the clinical and biological characteristics of this subset of melanoma patients in order to offer an individual treatment plan and prevent metastasis. Methods: We retrospectively analyzed melanoma patients with recurrence ≥10 years after a primary diagnosis documented between 1993 and 2012 at the skin cancer center of the University Medical Center Leipzig, Germany. We conducted a comprehensive review of the literature and compared the results with our data. Available archived primary melanoma tissue was investigated with a seven-marker immunohistochemical signature (immunoprint®) previously validated to reliably identify high-risk patients within stages IB-III. Results: Out of 36 analyzed patients, a third metastasized ultra-late (≥15 years). The mean age at initial diagnosis was 51 years, with women being diagnosed comparatively younger than men. The largest proportion of patients with late recurrence had primary melanomas located on the trunk. The immunoprint® signature of the available primary melanomas allowed the accurate prediction of a high risk. However, it is difficult to draw a definitive conclusion from the small number of cases that could be analyzed with immunoprint® (n = 2) in this study. Apart from the primary tumor characteristics, the laboratory values at time of metastasis, comorbidities and outcome are also shown. Conclusion: Late and ultra-late recurrent melanomas seem not to differ from melanomas in general, apart from a distinctly higher proportion of lower leg localizations in ultra-late recurrent melanomas. The immunoprint® signature may help to identify high-risk primary tumors at the time of initial diagnosis. However, apart from the risk profile of the primary tumor, it seems that individual immune surveillance can control residual tumor cells for more than a decade. Advanced age and increasing comorbidities may contribute to a disturbed immunological balance

Die kutane Autofluoreszenz als Risikofaktor und Prädiktor für renale Endpunkte bei Diabetes mellitus Typ 2

Die weltweite Prävalenz von Diabetes mellitus Typ 2 steigt stetig an. Gleichzeitig ist die diabetische Nephropathie die Hauptursache für end stage renal disease (ESRD) in Europa. Dennoch sind die genauen Mechanismen, die bei Diabetes mellitus zu renalen Schäden führen nicht klar erforscht. Die prospektive Kohortenstudie DIACORE (Diabetes Cohorte), in deren Rahmen diese Arbeit entstand, hat sich daher zum Ziel gesetzt, Ursachen und Mechanismen der Entstehung und Progression von Komplikationen und Spätfolgen bei Diabetes mellitus Typ 2 zu untersuchen. Eine wichtige Rolle bei der Entwicklung diabetischer Nephropathie spielen Advanced Glycation Endproducts (AGEs), glykierte Proteine, die durch den erhöhten Blutzuckerspiegel und gesteigerten oxidativen Stress bei Diabetikern vermehrt gebildet werden. Ziel dieser Arbeit ist herauszufinden, inwieweit die kutane Autofluoreszenz - als Maß für Advanced Glycation Endproducts - zum einen mit der prävalenten renalen Funktion und Albuminurie und zum anderen mit der Entwicklung renaler Funktionseinschränkungen bei Patienten mit Diabetes mellitus Typ 2 assoziiert ist. Hierzu wurde die kutane Autofluoreszenz bei 789 zufällig aus dem Gesamtkollektiv von 3000 Patienten der DIACORE-Studie ausgewählten Probanden zusätzlich zu dem standardisierten Studienprotokoll mit Hilfe des AGE-Readers gemessen. Alle rekrutierten Patienten leiden an Diabetes mellitus Typ 2. Nach der Baseline-Untersuchung bei Studieneinschluss folgten Follow-up-Untersuchungen nach 2 Jahre. Etwa 61% der Probanden in dem untersuchten Kollektiv sind männlich, das durchschnittliche Alter beträgt 66 Jahre bei einer mittleren Diabetesdauer von 10 Jahren. Es wurde im Durchschnitt ein kutaner Autofluoreszenzwert von 2,38 gemessen. In der Querschnittsanalyse konnte vor Adjustierung eine signifikante Korrelation der kutanen Autofluoreszenz mit der eGFR, der lnUACR sowie dem Vorliegen von Albuminurie und CKD aufgezeigt werden. Nach Einbeziehung der Kovariaten (Geschlecht, Alter, Diabetesdauer, HbA1c, WHR und aktueller Nikotin Abusus) konnte eine signifikante Assoziation der kutanen Autofluoreszenz hinsichtlich eGFR, lnUACR und Albuminurie bestätigt werden. Für die longitudinalen Berechnungen wurde der Zusammenhang der kutanen Autofluoreszenz mit bestimmten renalen Endpunkten (jährliche eGFR-Abnahme; Rapid5: jährliche eGFR-Abnahme um mindestens 5 ml/min/1,73m²; Rapid3: jährliche eGFR-Abnahme um mindestens 3 ml/min/1,73m²; CKDi25: Neuauftreten von CKD bei einer eGFR-Abnahme von mindestens 25%; Neuaufgetretene Albuminurie) in der Zeitspanne zwischen Baseline- und Follow-up-Untersuchung beleuchtet. In den univariaten Analysen konnte nur die signifikante Korrelation der Autofluoreszenz mit der Variablen CKDi25 gesehen werden. In den multivariaten Analysen (Kovariaten wie in Querschnittsanalyse, zusätzliche Adjustierung für Baseline-eGFR) konnte die kutane Autofluoreszenz für keinen der untersuchten Parameter als Risikofaktor identifiziert werden. Ein prädiktiver Wert der kutanen Autofluoreszenz für die Entwicklung renaler Komplikationen bei Diabetes mellitus Typ 2 kann in dieser Arbeit nicht nachgewiesen werden. Zukünftige prospektive Analysen der DIACORE-Studie unter Einbeziehung weiterer Daten und weiterer Follow-ups sollen mehr Aufschluss über die Assoziation der kutanen Autofluoreszenz mit der Nierenfunktion bei Diabetes mellitus und ihren prädiktiven Wert geben und so das Verständnis der zugrunde liegenden Pathophysiologie stärken

Compreensão dos familiares/cuidadores sobre segurança do paciente : subsídios para o cuidado seguro na oncologia pediátrica

Resumo não disponíve

Das Aufnahmeprogramm "Neustart im Team": Studie zur Programmumsetzung; Abschlussbericht

Zwischen 2019 und 2022 hat das Forschungszentrum des Bundesamts für Migration und Flüchtlinge (BAMF-FZ) die Umsetzung des staatlich-gesellschaftlichen Pilotprogramms NesT zur Aufnahme besonders schutzbedürftiger Geflüchteter evaluiert. Der Forschungsbericht 44 befasst sich mit den Ergebnissen der Evaluation. Das NesT-Programm ist Teil des deutschen Resettlement-Programms. Im Jahr 2023 ist die Aufnahme von bis zu 200 besonders schutzbedürftigen Flüchtlinge mit dem NesT-Programm vorgesehen. Im Resettlement und NesT werden Personen aufgenommen, die aus ihren Herkunftsländern geflohen sind und sich in sogenannten Erstzufluchtsstaaten aufhalten. Geflüchtete erhalten somit die Möglichkeit einer dauerhaften Lebensperspektive in Deutschland. Mit dem NesT-Programm werden besonders schutzbedürftige Geflüchtete von zivilgesellschaftlichen Akteurinnen und Akteuren - den sogenannten Mentoring-Gruppen - finanziell und ideell in Deutschland unterstützt. So stellen sie den Geflüchteten einen angemessenen Wohnraum zur Verfügung und übernehmen für zwölf Monate die Nettokaltmiete. Zudem erklären sie sich bereit, die aufgenommenen Personen mindestens ein Jahr mit Rat und Tat zu unterstützen. Eine eigens für das NesT-Programm eingerichtete Zivilgesellschaftliche Kontaktstelle (ZKS - bestehend aus Vertretern der Caritas, des Deutschen Roten Kreuzes und der Evangelischen Kirche von Westfalen) ist Ansprechpartnerin für Interessierte und entstandene Mentoring-Gruppen

Case Report: Graft Versus Tumor Effect After Non-Myeloablative Allogeneic Stem-Cell Transplantation in a Patient With Brentuximab-Vedotin Refractory Sezary Syndrome

Sezary Syndrome (SS) is a rare leukemic variant of primary cutaneous T-cell lymphoma. Relapsed or refractory disease is generally considered incurable by conventional therapeutic approaches, although durable responses can be achieved with novel monoclonal antibodies. Allogeneic hematopoietic stem cell transplantation (alloHSCT) may have potential value by inducing graft vs-lymphoma (GvL) effects, but there is currently no consensus regarding the timing of alloHSCT or type of conditioning regimen. Here we present the case of a male patient who achieved a complete remission (CR) of primary refractory SS after non-myeloablative alloHSCT. Patient: Two years prior to HSCT, the patient had been refractory to CHOEP-based chemotherapy, interferon, extracorporeal photopheresis (ECP), and bexarotene. Directly prior to alloHSCT brentuximab-vedotin (BV) was applied resulting in a partial remission of the skin compartment and overall in a stable disease. Prior to HSCT, flow cytometry of the bone marrow and peripheral blood showed an infiltration with T-cells positive for CD5, CD4, low CD3, low CD2 and negative for CD7, CD38, HLA-DR and CD8. The trephine biopsy showed a 7% infiltration of SS cells. The CD4:CD8 ratio in peripheral blood (pb) was massively increased at 76.67, with 63.5% of white blood cells expressing a SS immune phenotype. The conditioning regimen included 30 mg/m2 fludarabine on days -5, -4 and -3 and total body irradiation with 2 Gy on day -1. Immunosuppression consisted of cyclosporine A from day-1 and mycophenolate mofetil from day 0. The patient received 6.55x106 CD34+ cells and 1.11x108 CD3+ cells/kg body weight. Bone marrow evaluation on day 28 still showed persistent SS cells by flow cytometry. After tapering immunosuppression until day 169, the CD4:CD8 ratio in pb normalized. CR was documented on day 169 after alloHSCT and is now ongoing for almost 3 years after alloHSCT. Conclusions: We confirm that an alloHSCT can be a curative option for refractory patients with SS. The achievement of a CR after tapering the immunosuppressive therapy indicates a significant role of the GvL effect. In present treatment algorithms for patients with SS, the timing of an alloHSCT and the intensity of conditioning should be further explored

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Navigating between Structure and Agency: Moroccan Independent Youth Migration

Recent International Migration Scholarship is slowly moving away from the tendency to predominantly focus on adult migration. Awareness has widened that young migrants engage in migration for similar reasons as adult migrants, and one of these reasons can be economic. Over the past 2 decades, an increasing number of unaccompanied minors have migrated on dangerous routes to the Western world for reasons that can often not be clearly categorised under current legal and policy definitions. Whereas International Development Scholarship is well aware of children and adolescents migrating South-South for reasons other than war, persecution, and child trafficking, economic youth migration was rarely acknowledged with South-North migration. Moroccan children and adolescents, usually males between 14 and 16 years of age, but sometimes much younger, were among the first to have engaged in independent migration to Europe since the early 2000s. They first arrived in Spain (and some in Italy), and became quickly known for moving onward north, until they were sighted about a decade and a half later for the first time in Sweden. Regardless of which European country they migrated to, authorities were in general stupefied by the independent and mature manner in which they absconded from or avoided reception structures altogether and not seldom became associated with delinquencies. Through the lens of a Theory of Practice combined with World Systems Analysis, supported by ethnographic fieldwork, the present research investigates the reasons why young Moroccans engage in independent youth migration, how they put their migration into practice and their reasons for onward migration within Europe. It looks at the structural constraints and opportunities the young migrants face in Morocco, in terms of a particular emigration culture that has been shaped historically, and present-day conditions in Morocco which influence the decision why some of their youth leave the country under the most dangerous conditions of contemporary migration. Moroccan children and adolescents migrate with a utopic migration goal imagining that they will better their lives and that of their families by migrating to Europe and become providers, regardless their age. Yet, the young migrants are confronted with enabling and constraining structures also once they arrive in Europe, which are predominantly of legal and policy origin. Unaccompanied minors are defined as children and victims due to a particular social construction of childhood, and within the context of the Refugee Convention. Young Moroccans are in general unable and unwilling to fit this particular profile, but due to the fact that they are children, they are tolerated to stay in Europe until the age of 18. These structures are incorporated into their migration project while they organize themselves in groups, or Communities of Practice, that are crucial for their survival and information sharing. These groups are however not always beneficial. Psychological instability, disappointment and inability to understand the controversies of Western society, can lead to a desocialising spiral where they are increasingly marginalised. Moroccan independent youth migrants are navigating between structure and agency, shaping their migration from Morocco to Europe and within Europe, making them vulnerable in ways beyond legal and policy definitions they fall under as unaccompanied minors

Geschäftsfeldanalyse und Strategieentwicklung für "Spezialgetreide" am Beispiel des Unternehmens BARO Lagerhaus GmbH und Co. KG in Dänemark

Object of the investigation of this masterthesis is the analysis of the market segment cereals- "Produced under special conditions" (Spezialgetreide) in Denmark. The medium sized agricultural trading company BARO Lagerhaus GmbH & Co. KG is already operating in this special segment will be investigated by the help of common methodes of the strategic management on business unit level. One major objective is the analysis and discription of the current situation at the target market, in gerneral but also of the agricultural-, grain-milling and baking industry in particular. Subseqently, the specific internal performance-analysis of the strength and weaknesses - of the BARO business unit will be determined. Finally, model based scenarios will be developed which support the establishment of strategies that contribute to an successful an long lasting market position of the BARO- business unit.Untersuchungsgegenstand der vorliegenden Abschlussarbeit ist die Analyse des dänischen Marktsegments Getreide „produziert nach besonderen Anbaubedingungen“. Für die BARO Lagerhaus GmbH & Co. KG, einem mittelständischen landwirtschaftlichen Erfassungshändler, welcher das „Spezialsegment“ im Exportgeschäft bedient, werden mit Hilfe klassischer Methoden des strategischen Managements auf Geschäftsfeldebene die Ausgangssituation - die herrschenden Bedingungen am Zielmarkt allgemein sowie die Branchengegebenheiten im speziellen - analysiert und beschrieben. Anschließend wird die spezifische interne Leistungsfähigkeit des BARO-Geschäftsfeldes durch Zuhilfenahme der Methode der Stärken/Schwächenanalyse ermittelt. Darauf aufbauend werden mittels eines modellgestützten Ansatzes der Szenario-Entwicklung Vorschläge für Strategien formuliert, welche dazu beitragen, das Geschäftsfeld nachhaltig erfolgreich am dänischen Zielmarkt zu positionieren