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Despite laws for non-discriminatory medical care, people with disabilities often perceive their primary care as insufficient. They report barriers to access and uncertainties among medical staff. The aim of this study was to examine the primary care situation for people with disabilities in Munich. In this cross-sectional study, between August and October 2024, people with disabilities in Munich were surveyed about their primary care experience using a questionnaire. No exclusion criteria were applied. The survey was conducted both online and in written form, using plain- and easy-to-read language. Data were analyzed using descriptive statistics, and bivariate analyses were conducted to examine associations. Logistic regression analysis was used to calculate predictors for the likelihood of having or having had difficulties in finding a general practitioner. A total of 306 people participated in the survey; 95% (n=291) reported having a GP, and over 80% were satisfied with medical (n=253) and practice staff (n=252). Nevertheless, 39% (n=111) reported difficulties in finding a GP, and 33% (n=91) had been refused by a practice at least once. Differences in care were observed regarding the utilization of appointments, the need to visit a GP due to disability, difficulties in finding a medical practice, freedom of choice of physician, and acceptance into a GP practice, depending on gender, living situation, and type of disability, as well as with regard to the need for home visits. In addition, multivariate analyses showed that people with disabilities had a significantly higher risk of experiencing difficulties in finding a GP if they had previously been refused by a practice, were restricted during medical visits, or needed home visits. The study shows that, from the perspective of people with disabilities, primary care was rated as satisfactory; however, access problems persist due to structural, communication and social barriers. The results can help provide stakeholders with practical arguments to improve the care situation. Trotz gesetzlicher Vorgaben zur diskriminierungsfreien ärztlichen Versorgung empfinden Menschen mit Behinderungen (MmB) ihre hausärztliche Versorgung häufig als unzureichend. Sie berichten von Barrieren beim Zugang zur Versorgung und Unsicherheiten des medizinischen Personals. Während Kinder in sozialpädiatrischen Zentren betreut werden, gibt es für Erwachsene mit Behinderungen keine Alternativen. Zwar etablieren sich Medizinische Zentren für Erwachsene mit Behinderungen, allerdings sind diese nicht dafür gedacht, Mängel in der ambulanten Versorgung von MmB abzufangen. Ziel dieser Studie war es, die hausärztliche Versorgungssituation von MmB aus Sicht der MmB in München zu untersuchen.In einer Querschnittstudie wurden MmB ohne Ausschlusskriterien in München mittels eines Fragebogens von August bis Oktober 2024 zu ihrer hausärztlichen Versorgung befragt. Die Befragung konnte in Alltags- und leichter Sprache online und schriftlich durchgeführt werden. Mit Hilfe deskriptiver Statistik und bivariater Analysen wurden Häufigkeiten und Zusammenhänge untersucht. Durch eine logistische Regressionsanalyse wurden Prädiktoren für die Wahrscheinlichkeit, Schwierigkeiten bei der Suche nach einem Hausarzt zu haben oder gehabt zu haben berechnet.An der Befragung nahmen 306 Personen teil. Davon gaben 95% (n=291) an, eine Hausärztin/ einen Hausarzt zu haben und über 80% waren mit ärztlichem (n=253) bzw. Praxispersonal (n=252) zufrieden. Dennoch berichteten 39% (n=111) von Schwierigkeiten bei der Ärztin-/Arztsuche und 33% (n=91) wurden schon einmal von einer Praxis abgewiesen. Es zeigten sich Unterschiede in der Versorgung hinsichtlich der Inanspruchnahme von Terminen, der Notwendigkeit des Besuches des Hausarztes/ der Hausärztin aufgrund der Beeinträchtigung, Schwierigkeiten bei der Suche nach einer ärztlichen Praxis sowie bei der freien Ärztin/Arztwahl und der Aufnahme in eine hausärztliche Praxis, in Abhängigkeit von Geschlecht, Wohnform und Art der Beeinträchtigung sowie bei der Notwendigkeit von Hausbesuchen. Zudem ergaben die multivariaten Analysen, dass MmB ein signifikant höheres Risiko für Schwierigkeiten bei der Suche nach einer Hausärztin/ einem Hausarzt haben, wenn sie schon einmal von einer Praxis abgewiesen wurden, beim Arztbesuch eingeschränkt sind oder Hausbesuche benötigen.Die Studie zeigt, dass die hausärztliche Versorgung aus Sicht der MmB als zufriedenstellend eingestuft wurde, jedoch Zugangsprobleme aufgrund baulicher, sprachlicher sowie sozialer Barrieren bestehen. Sie bietet erste Ergebnisse und Hinweise auf daraus entstehende Herausforderungen bei Hausarztbesuchen. Die Ergebnisse können dazu beitragen, Akteur*innen praxisnahe Argumente für eine Verbesserung der Versorgungssituation zu liefern.

Antimicrobial resistance poses a significant threat to global health, with Gram-negative pathogens contributing to morbidity, mortality and healthcare costs. While ceftolozane/tazobactam provides an effective treatment option against these pathogens, real-world data on healthcare resource use associated with ceftolozane/tazobactam, especially outside the USA, remain limited. This retrospective, multinational observational study includes 617 adult inpatients from Australia, Austria, Germany, Italy, Mexico, Spain and the UK who received ≥48 hours of ceftolozane/tazobactam. The outcomes included 30-day all-cause and infection-related readmission rates, hospital length of stay and post-ceftolozane/tazobactam length of stay. Subgroup analyses were conducted by rank of ceftolozane/tazobactam initiation, ICU admission and cystic fibrosis status. The overall 30-day all-cause readmission rate was 10.2%. The infection-related readmission rate was 4.9%. The median hospital length of stay was 42 days (IQR 22-71), and median post-ceftolozane/tazobactam length of stay was 6 days (IQR 1-25). Among ICU patients (n = 298), the 30-day all-cause readmission rate was 3.4% and median length of stay was 59 days. In cystic fibrosis patients (n = 64), the 30-day all-cause readmission rate was 10.9% and the median length of stay was 31.5 days (IQR 16-48.5). This is the largest multinational, real-world dataset on healthcare resource use associated with ceftolozane/tazobactam outside the USA. These descriptive findings show differences in readmission rates and length of stay across rank-of-initiation groups; however, no causal relationships can be inferred from these data. The results are hypothesis-generating for future adjusted and economic analyses. Further research is warranted for economic evaluations and to optimize the timing of ceftolozane/tazobactam initiation.

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Ten-eleven translocation (TET) enzymes are critical epigenetic regulators, which oxidize the methylated cytosine nucleobase 5-methyl-dC (mdC) in the genome to 5-hydroxymethyl-dC (hmdC) in an α-ketoglutarate-dependent manner. Because the presence of mdC in the promoter region of a given gene silences its expression, this oxidation goes in hand with the reactivation of such silenced genes. In different highly aggressive cancers such as acute myeloid leukemia (AML) and glioblastoma, loss of TET enzyme function, and therefore reduced hmdC levels pave the way for tumor development. Impairment of TET activity can occur through metabolic inhibition, through loss-of-function mutations in TET genes themselves, and finally through suppression of TET-expression via epigenetic silencing. Reactivation of TET enzyme expression represents a major aim of epigenetic cancer therapy. Here we show that the carbocyclic antimetabolite 5-aza-2'deoxycytidine (cAzadC), which is supposed to suppress the methylation of DNA during replication, leads to a substantial increase of TET2 expression and strongly increasing hmdC levels. We show that the treatment with cAzadC goes in hand with the broad reactivation of the cellular antitumor responses. With patient-derived xenograft AML-mouse models, we show that this translates into a strongly improved anticancer effect in vivo.

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Examination of personal, job-related, and organizational resources of professional and managerial staff in disability services when working with people with intellectual disabilities and challenging behavior. Online survey (n=279) on working conditions, experiences of aggression, stress, resources, and work-related sense of coherence; hierarchical multiple regression analysis to identify predictors of professionals' work-related sense of coherence. Work-related sense of coherence was more strongly associated with perceived resources, structural conditions, and job satisfaction than with adverse events (experienced verbal and physical aggression; psychological stress symptoms). Team cohesion and exchange, appreciation, and clear roles and structures were highlighted as key resources. Measures to promote team cohesion, reliable staffing, and an appreciative, clearly structured organizational culture are essential. Untersuchung der personalen, arbeitsbezogenen und organisationalen Ressourcen von Fach- und Leitungskräften in der Eingliederungshilfe bei der Arbeit mit Menschen mit intellektuellen Beeinträchtigungen und herausforderndem Verhalten. Onlinebefragung (n=279) zu Arbeitsbedingungen, Aggressionserfahrungen, Stress, Ressourcen und arbeitsbezogenem Kohärenzgefühl; hierarchische multiple Regressionsanalyse zu Prädiktoren des arbeitsbezogenen Kohärenzgefühls der Fachkräfte. Das arbeitsbezogene Kohärenzgefühl hängt stärker mit der Wahrnehmung von Ressourcen, strukturellen Rahmenbedingungen und Arbeitszufriedenheit zusammen als mit belastenden Ereignissen (erlebte verbale und physische Aggressionen; psychische Stresssymptome). Teamzusammenhalt und Austausch, Wertschätzung, klare Rollen und Strukturen wurden als wichtige Ressourcen hervorgehoben. Maßnahmen zur Förderung von Teamzusammenhalt, verlässlicher Personalausstattung und wertschätzender, klar strukturierter Organisationskultur sind zentral.

National income level influences the prevalence and outcomes of cardiovascular disease (CVD), with lower-income countries contributing disproportionately to the global CVD burden. Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) requires specialised equipment, increasing procedural costs. However, whether national income level contributes to disparities in managing patients with CTO remains unclear. To compare the clinical profiles, procedural settings and outcomes of patients undergoing CTO-PCI in middle-income countries (MICs) and high-income countries (HICs). This cross-sectional study included 15,329 patients who underwent CTO-PCI between 2021 and 2023. Data were obtained from the European Registry of Chronic Total Occlusions (ERCTO). Of the 24 enrolling countries, 7 were classified as MICs and 14 as HICs. Patients in HICs were older (67&#x202f;&#xb1;&#x202f;10 vs 61&#x202f;&#xb1;&#x202f;10&#x202f;years; p&#x202f;<&#x202f;0.001) and presented with greater CTO complexity (J-CTO score: 2.31&#x202f;&#xb1;&#x202f;1.25 vs 1.99&#x202f;&#xb1;&#x202f;1.17; p&#x202f;<&#x202f;0.001). Conversely, patients in MICs were more likely to have diabetes (35% vs 29%; p&#x202f;<&#x202f;0.001) and to be active smokers (59% vs 49%; p&#x202f;<&#x202f;0.001). Patients in MICs had lower use of mechanical cardiac support (0.1% vs 0.8%; p&#x202f;<&#x202f;0.001), advanced calcific plaque modification devices (1% vs 6.1%; p&#x202f;<&#x202f;0.001), and intravascular ultrasound (14% vs 25%; p&#x202f;<&#x202f;0.001). MICs achieved higher procedural success (89.5% vs 90.5%; p&#x202f;=&#x202f;0.07) but higher mortality compared to HICs (0.6% vs 0.2%; p&#x202f;<&#x202f;0.001). Among a selected population of patients undergoing CTO-PCI, notable clinical, anatomical, and procedural differences exist between MICs and HICs. These findings highlight the importance of tailoring public health strategies to optimise cardiovascular care across diverse economic settings.

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Obesity increases the risk of common diseases and mortality, placing a significant burden on our aging society. Bariatric surgery results in significant weight loss; however, the amount of associated health gain is currently less studied, particularly in the first two years. We modelled mortality-associated biological age according to established blood markers in a prospective cohort of 505 patients that underwent bariatric surgery. The difference between biological age and chronological age (age acceleration) as a molecular marker of health gain was evaluated at different time points with mixed effects models. At baseline, biological age acceleration was positively correlated to higher smoking exposure as well as increased body mass, particularly in males. Twelve months after surgery, patients were on average 5.55 years younger (slope and 95% confidence intervals (95% CI): -5.55 [-6.12; -4.97]) which remained stable until 24 months. When adjusted for changes in body mass index over time, the effect seizes decreased to 3.32 years younger age at 12 months post-surgery (slope and 95% CI: -3.32 [-4.26; -2.37]), indicating an age-rejuvenating effect - more pronounced in men - beyond weight loss. Individual markers such as glucose and C-reactive protein levels as well as blood cell counts contributing to biological age computation showed a generally more favorable change after surgery. In conclusion, biological age was markedly reduced in patients undergoing bariatric surgery resulting in a 40-50% reduction in expected mortality after two years, particularly in men. Our findings support the use of biological age as a clinically meaningful, patient-centered marker of treatment success after bariatric surgery.

Digital transformation is fundamentally reshaping dermatology, creating new opportunities in diagnostics, therapy, and healthcare organization. Large datasets combined with Artificial Intelligence (AI) enable more precise classification and prognosis, particularly through the analysis of clinical and dermoscopic imaging. Increasingly, synthetically generated data is used to train new algorithms, though its clinical validity remains under evaluation. Teledermatology has established itself as an integral part of care. Video consultations and asynchronous image transfers enhance accessibility to dermatological expertise and can bridge care gaps, especially in structurally weak regions. Furthermore, mobile applications and digital platforms promote adherence, self-monitoring, and active patient engagement. Despite these opportunities, challenges regarding data protection, interoperability, and regulatory frameworks must be addressed to ensure sustainable implementation. Interdisciplinary collaboration between medicine, technology, and health economics is crucial. Physicians play a central role as subject matter experts in assessing data quality and providing clinical interpretation of digital systems. Continuous training of medical staff remains essential. Overall, digitalization offers significant potential to improve dermatological care, provided there are structured processes, quality assurance, and consistent patient involvement.

Despite improved survival in recent years, long-term outcomes in patients surviving progressive multifocal leukoencephalopathy beyond the first year remain poorly defined. This international multicenter retrospective study aimed to characterize the three-year prognosis of patients with progressive multifocal leukoencephalopathy who had survived at least one year, identify factors associated with favorable outcomes and late mortality, and determine recurrence rate. Data were collected through standardized questionnaires across forty-one centers in twelve countries. Patients were eligible if they met the 2013 diagnostic criteria for definite progressive multifocal leukoencephalopathy of the American Academy of Neurology, survived at least one year after diagnosis, and had documented follow-up three years after diagnosis. Demographic, clinical, virological, and radiological data were retrieved at diagnosis, one year, and three years. Functional status was assessed using the modified Rankin Scale, with scores of 0-2 defining a favorable outcome. Generalized linear mixed models identified independent predictors of three-year functional status and late mortality. Among 1877 screened cases, 245 patients met inclusion criteria. The most common underlying causes of immunosuppression were HIV infection (48%), autoimmune/inflammatory diseases (26%), and hematological malignancies (18%). At three years, 220 patients (89.8% of the cohort) were alive and 188 (85.5% of survivors) had neurological sequelae, most frequently motor or cognitive impairment. Overall, 112/245 (45.7%) achieved a favorable functional outcome. HIV-associated progressive multifocal leukoencephalopathy (OR 2.36, 95% CI 1.05-5.28) was associated with a favourable outcome, whereas higher modified Rankin Scale score at diagnosis (OR 0.48, 95% CI 0.35-0.66) and higher number of affected brain regions on baseline MRI (OR 0.78, 95% CI 0.64-0.95) were independently associated with poorer functional outcome. Among variables collected one year after diagnosis, good functional status at that time was significantly associated with long-term favorable outcome (OR 0.01, 95% CI <0.01-0.03). Twenty-five patients (10.2%) died after the first year, with mortality associated with higher lesion burden at diagnosis and primary immunodeficiency as underlying disease. Even beyond the first year, progressive multifocal leukoencephalopathy remained the leading cause of death (11/25). Recurrence occurred in seven patients (2.9%) and was almost always fatal (6/7). This study provides a comprehensive evaluation of long-term outcomes among survivors of progressive multifocal leukoencephalopathy. These findings present a nuanced picture: while most remain neurologically impaired, nearly half achieve functional independence at three years. The results emphasize the prognostic relevance of the initial clinical and radiological burden and early functional trajectory and highlight the need for research into mechanisms driving disease recurrence.

Medical ultrasound education is evolving, embracing various teaching methods such as classical, e-learning, and hands-on approaches. The integration of ultrasound into medical school curricula has highlighted the importance of blended learning, although there is limited literature on specific learning theories and pedagogical concepts. Medical ultrasound learning is unique, requiring psychomotor and technical skills in probe handling, anatomical and clinical knowledge, and cognitive abilities for image interpretation. A review of literature in a systematic way was conducted across multiple databases, including PubMed, Embase, and Scopus, using predefined search terms such as "ultrasound education," "e-learning," "simulation-based ultrasound," and "peer-assisted learning ultrasound." The search targeted studies focusing on undergraduate medical education and ultrasound instruction. Following duplicate removal, two independent reviewers screened titles and abstracts, with eligible full-text articles assessed against inclusion criteria. Studies were included if they addressed didactic ultrasound teaching methods and reported on educational outcomes relevant to medical students or trainees. The inverted classroom approach, where preparatory material is studied before class, was effective in ultrasound education. Blended learning, an educational approach that combines traditional classroom instruction with online learning activities and resources, enhanced both cognitive understanding and practical skills. Simulation-based training emerged as valuable, providing safe environments for learning and is applicable across pre-clinical and clinical phases. The study also assessed the advantages and limitations of simulation-based training and e-learning. The paper highlights the need for diverse teaching methodologies in ultrasound education. It emphasizes that while traditional methods may be cost-effective, modern approaches, such as blended learning and simulation-based training, offer more engaging, practical, and efficient learning experiences. Integrating these methods within existing curricula enhances ultrasound training quality, advocating for an interdisciplinary and technologically adapted approach. The study concludes that a blend of traditional and contemporary teaching methods, including e-learning and simulation, is essential for effective ultrasound education in medical studies. Adapting to technological advancements and diverse learning styles is crucial in preparing students for modern healthcare demands.

The pathogenesis of Parkinson's disease is multifactorial, but disruption of calcium and iron is a common feature. The mitochondrial Rho GTPase Miro1 is a component of the mitochondrial-endoplasmic reticulum contact sites and a key regulator of calcium homeostasis. Heterozygous variants in the Miro1-encoding gene RHOT1 were identified in Parkinson's disease patients. Neurons harboring Parkinson's disease-associated variants show defects in mitochondrial calcium regulation and mitochondria-ER contact sites organization which we hypothesize to contribute to neuronal vulnerability. However, the exact mechanism is not fully understood. We systematically assessed the role of Miro1 and its different domains by using a set of isogenic lines with gene edited mutations S156A and K572R in PINK1/Parkin regulatory elements and the Parkinson's disease-associated mutation R272Q. This showed us a general role of Miro1 in the regulation of cellular calcium homeostasis and the regulation of mitochondrial-ER contact sites, but more importantly, a domain-specific involvement of local calcium distribution, impaired store operated calcium entry and vulnerability to ferroptosis. These findings indicate that Miro1-mutant specific impairments in cellular calcium handling contributes to neuronal vulnerability via mitochondria-ER contact sites and provides further insights in the mechanism how impaired regulation of Miro1 impacts neurons in the context of Parkinson's disease.

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The long-term viability of kidney transplantation is commonly hindered by initial ischemia-reperfusion injury (IRI) and the ensuing T cell-mediated rejection (TCMR). Upon reperfusion, the inevitable IRI provokes an acute surge of reactive oxygen species (ROS), thereby driving profound tubular ferroptosis. Dying cells release damage-associated molecular patterns (DAMPs) that attract alloreactive T cells, intensifying oxidative stress and ferroptosis in a destructive feedback loop. To alleviate the severity of TCMR, we developed ultra-small black phosphorus quantum dots (BPQD) loaded with ferrostatin-1, a ferroptosis inhibitor (BPQD@Fer-1 nanoparticles) delivered directly via ex vivo graft perfusion. Owing to its ultra-small size, BPQD@Fer-1 efficiently accumulates within the renal tubules. This pre-arming strategy enables BPQD@Fer-1 to provide an immediate, synergistic defense: simultaneously quenching the initial ROS storm and blocking downstream lipid peroxidation. In a rat transplant model, preventing early tubular ferroptosis effectively silences DAMP release and cuts off recruitment signals for host T cells. Consequently, BPQD@Fer-1 sharply reduces CD8+ T cell infiltration, demonstrating that preemptive ex vivo protection effectively circumvents subsequent immune rejection.

The anesthesiological care of children places particular demands on the knowledge and skills of the anesthetist providing care. There is currently no structured further training in this field in Germany. A&#xa0;curriculum for a&#xa0;fellowship program in pediatric anesthesiology was developed through a&#xa0;consensus procedure. Building on specialist anesthesiology training this program aims to impart specific knowledge and skills for the care of children. The defined final skills were divided into basic and advanced skills. Basic skills are taught at all fellowship sites, while the teaching of advanced skills depends on the structural requirements of the centers. In addition to the acquisition of clinical competencies, the fellowship comprises mandatory supplementary components, such as a&#xa0;quality improvement project, continuing professional development, certified pediatric emergency courses and webinars. The fellows' progress in competencies is monitored through regular, standardized evaluation interviews and documented as part of a&#xa0;structured evaluation. The "Pediatric Anesthesiology Fellowship" is a&#xa0;competency-based, curriculum-structured training program. Building on specialist anesthesiology training it aims to contribute to the sustainable improvement of patient safety and the quality of care in pediatric anesthesiology. EINLEITUNG: Die an&#xe4;sthesiologische Versorgung von Kindern stellt besondere Anforderungen an die Kenntnisse und Kompetenzen der betreuenden An&#xe4;sthesist:innen. In Deutschland existiert derzeit keine strukturierte Weiterbildung in diesem Bereich. Im Rahmen eines Konsensusverfahrens wurde ein Curriculum f&#xfc;r ein Fellowship-Programm in der Kinderan&#xe4;sthesiologie entwickelt. Aufbauend auf der an&#xe4;sthesiologischen Facharztweiterbildung soll dieses Programm spezifische Kenntnisse und Kompetenzen f&#xfc;r die Versorgung von Kindern vermitteln. Die definierten Abschlussfertigkeiten wurden in Basis- und erweiterte Fertigkeiten unterteilt. Basisfertigkeiten werden an allen Fellowship-Standorten vermittelt, w&#xe4;hrend die Vermittlung der erweiterten Fertigkeiten von den strukturellen Voraussetzungen der Zentren abh&#xe4;ngt. Erg&#xe4;nzend zum klinischen Kompetenzerwerb umfasst das Fellowship verpflichtende Zusatzbausteine wie eine qualit&#xe4;tsverbessernde Projektarbeit, Fortbildungen, zertifizierte Kindernotfallkurse und Webinare. Der Kompetenzfortschritt der Fellows wird durch regelm&#xe4;&#xdf;ige, standardisierte Evaluationsgespr&#xe4;che begleitet und im Rahmen einer strukturierten Evaluation dokumentiert. Das &#x201e;Fellowship Kinderan&#xe4;sthesiologie&#x201c; ist ein kompetenzbasiertes, curricular aufgebautes Weiterbildungsprogramm. Aufbauend auf der an&#xe4;sthesiologischen Facharztweiterbildung soll es dazu beitragen, die Patientensicherheit und Versorgungsqualit&#xe4;t in der an&#xe4;sthesiologischen Versorgung von Kindern nachhaltig zu verbessern.