Zur Situation gehörloser Menschen im Alter (SIGMA)

In dem Projekt SIGMA wurden im Auftrag des Bundesministeriums für Familie, Senioren, Frauen und Jugend erstmals aus der Perspektive gehörloser Menschen im Alter ihre individuellen Ressourcen sowie die Qualität und Quantität von Angeboten und Maßnahmen der Altenhilfe erforscht. Zwischen 2006 und 2009 wurden u.a. mehr als 200 gehörlose Menschen über 55 Jahre zu ihren spezifischen Lebensbedingungen und Lebensvorstellungen interviewt. Darüber hinaus wurden auch Experten zu der Versorgungssituation der Zielgruppe befragt. Die Ergebnisse belegen, dass für gehörlose Menschen auch im Alter der Kontakt zur Gehörlosengemeinschaft neben der Familie die zentrale soziale Ressource bildet. Sobald hier die Teilhabe aufgrund eingeschränkter Mobilität nicht mehr möglich ist, sind gehörlose Menschen besonders von Vereinsamung bedroht. Gehörlosen Menschen stehen von wenigen Ausnahmen abgesehen keine spezifischen Angebote zur Verfügung, die ihre sprachlichen und kulturellen Bedürfnisse angemessen berücksichtigen. Insbesondere Angebote der medizinischen und ambulanten Ver­sor­gung sowie Altenwohnheime, die hörenden Menschen zur Verfügung stehen, sind auf die kommunikativen Anforderungen gehörloser Menschen nicht vorbereitet

Plasmodium falciparum:Rosettes do not protect merozoites from invasion-inhibitory antibodies

Rosetting is a parasite adhesion phenotype associated with severe malaria in African children. Why parasites form rosettes is unknown, although enhanced invasion or immune evasion have been suggested as possible functions. Previous work showed that rosetting does not enhance parasite invasion under standard in vitro conditions. We hypothesised that rosetting might promote invasion in the presence of host invasion-inhibitory antibodies, by allowing merozoites direct entry into the erythrocytes in the rosette and so minimising exposure to plasma antibodies. We therefore investigated whether rosetting influences invasion in the presence of invasion-inhibitory antibodies to MSP-1. We found no difference in invasion rates between isogenic rosetting and non-rosetting lines from two parasite strains, R29 and TM284, in the presence of MSP-1 antibodies (P=0.62 and P=0.63, Student's t test, TM284 and R29, respectively). These results do not support the hypothesis that rosettes protect merozoites from inhibitory antibodies during invasion. The biological function of rosetting remains unknown

Sarcoma classification by DNA methylation profiling in clinical everyday life: the Charité experience

Background: Sarcomas are a heterogeneous group of rare malignant tumors with more than 100 subtypes. Accurate diagnosis remains challenging due to a lack of characteristic molecular or histomorphological hallmarks. A DNA methylation-based tumor profiling classifier for sarcomas (known as sarcoma classifier) from the German Cancer Research Center (Deutsches Krebsforschungszentrum) is now employed in selected cases to guide tumor classification and treatment decisions at our institution. Data on the usage of the classifier in daily clinical routine are lacking. Methods: In this single-center experience, we describe the clinical course of five sarcoma cases undergoing thorough pathological and reference pathological examination as well as DNA methylation-based profiling and their impact on subsequent treatment decisions. We collected data on the clinical course, DNA methylation analysis, histopathology, radiological imaging, and next-generation sequencing. Results: Five clinical cases involving DNA methylation-based profiling in 2021 at our institution were included. All patients' DNA methylation profiles were successfully matched to a methylation profile cluster of the sarcoma classifier's dataset. In three patients, the classifier reassured diagnosis or aided in finding the correct diagnosis in light of contradictory data and differential diagnoses. In two patients with intracranial tumors, the classifier changed the diagnosis to a novel diagnostic tumor group. Conclusions: The sarcoma classifier is a valuable diagnostic tool that should be used after comprehensive clinical and histopathological evaluation. It may help to reassure the histopathological diagnosis or indicate the need for thorough reassessment in cases where it contradicts previous findings. However, certain limitations (non-classifiable cases, misclassifications, unclear degree of sample purity for analysis and others) currently preclude wide clinical application. The current sarcoma classifier is therefore not yet ready for a broad clinical routine. With further refinements, this promising tool may be implemented in daily clinical practice in selected cases

Comprehensive metabolic profiling of chronic low-grade inflammation among generally healthy individuals.

BACKGROUND: Inflammation occurs as an immediate protective response of the immune system to a harmful stimulus, whether locally confined or systemic. In contrast, a persisting, i.e., chronic, inflammatory state, even at a low-grade, is a well-known risk factor in the development of common diseases like diabetes or atherosclerosis. In clinical practice, laboratory markers like high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen, are used to reveal inflammatory processes. In order to gain a deeper insight regarding inflammation-related changes in metabolism, the present study assessed the metabolic patterns associated with alterations in inflammatory markers. METHODS: Based on mass spectrometry and nuclear magnetic resonance spectroscopy we determined a comprehensive panel of 613 plasma and 587 urine metabolites among 925 apparently healthy individuals. Associations between inflammatory markers, namely hsCRP, WBC, and fibrinogen, and metabolite levels were tested by linear regression analyses controlling for common confounders. Additionally, we tested for a discriminative signature of an advanced inflammatory state using random forest analysis. RESULTS: HsCRP, WBC, and fibrinogen were significantly associated with 71, 20, and 19 plasma and 22, 3, and 16 urine metabolites, respectively. Identified metabolites were related to the bradykinin system, involved in oxidative stress (e.g., glutamine or pipecolate) or linked to the urea cycle (e.g., ornithine or citrulline). In particular, urine 3'-sialyllactose was found as a novel metabolite related to inflammation. Prediction of an advanced inflammatory state based solely on 10 metabolites was well feasible (median AUC: 0.83). CONCLUSIONS: Comprehensive metabolic profiling confirmed the far-reaching impact of inflammatory processes on human metabolism. The identified metabolites included not only those already described as immune-modulatory but also completely novel patterns. Moreover, the observed alterations provide molecular links to inflammation-associated diseases like diabetes or cardiovascular disorders

Surgical Margins in Soft Tissue Sarcoma Management and Corresponding Local and Systemic Recurrence Rates: A Retrospective Study Covering 11 Years and 169 Patients in a Single Institution

Soft tissue sarcomas (STSs) are a diverse group of rare malignant soft tissue tumors with a high disease burden. Treatment protocols are complex and, to this day, a precise recommendation for the surgical margin width is lacking. The present study aims to analyze the width of the surgical margins in STS resection specimens and analyze them for local and systemic disease-free survival as well as for most frequent histologic STS subtypes. A total of 169 consecutive patients diagnosed and treated in curative intent in our institution following a primary and localized STS of the extremities or trunk from January 2010 to December 2020 were included in this study regardless of age. Our data reveal that low-grade STSs are best controlled locally by a surgical margin >= 2 mm and in this way also preventing distant metastases effectively. Local recurrence-free survival and metastasis-free survival in high-grade STS were improved by intact muscle fascia or periosteum at the margin when compared only to soft tissue. However, the outcome was independent of the surgical margin width, suggesting a close but negative margin may be safe in high-grade STS subtypes with less invasive growth patterns when combined with adjunct radiochemotherapy

Preoperative hypofractionated radiotherapy for soft tissue sarcomas: a systematic review

Background: Soft tissue sarcomas (STS) represent a diverse group of rare malignant tumors. Currently, five to six weeks of preoperative radiotherapy (RT) combined with surgery constitute the mainstay of therapy for localized high-grade sarcomas (G2-G3). Growing evidence suggests that shortening preoperative RT courses by hypofractionation neither increases toxicity rates nor impairs oncological outcomes. Instead, shortening RT courses may improve therapy adherence, raise cost-effectiveness, and provide more treatment opportunities for a wider range of patients. Presumed higher rates of adverse effects and worse outcomes are concerns about hypofractionated RT (HFRT) for STS. This systematic review summarizes the current evidence on preoperative HFRT for the treatment of STS and discusses toxicity and oncological outcomes compared to normofractionated RT. Methods: We conducted a systematic review of clinical trials describing outcomes for preoperative HFRT in the management of STS using PubMed, the Cochrane library, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Embase, and Ovid Medline. We followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Trials on retroperitoneal sarcomas, postoperative RT, and hyperthermia were excluded. Articles published until November 30th, 2021, were included. Results: Initial search yielded 94 articles. After removal of duplicate and ineligible articles, 13 articles qualified for analysis. Eight phase II trials and five retrospective analyses were reviewed. Most trials applied 5 x 5 Gy preoperatively in patients with high-grade STS. HFRT courses did not show increased rates of adverse events compared to historical trials of normofractionated RT. Toxicity rates were mostly comparable or lower than in trials of normofractionated RT. Moreover, HFRT achieved comparable local control rates with shorter duration of therapy. Currently, more than 15 prospective studies on HFRT + / - chemotherapy are ongoing. Conclusions: Retrospective data and phase II trials suggest preoperative HFRT to be a reasonable treatment modality for STS. Oncological outcomes and toxicity profiles were favorable. To date, our knowledge is mostly derived from phase II data. No randomized phase III trial comparing normofractionated and HFRT in STS has been published yet. Multiple ongoing phase II trials applying HFRT to investigate acute and late toxicity will hopefully bring forth valuable findings

The role of neoadjuvant radiochemotherapy in the management of localized high-grade soft tissue sarcoma

Background: Standard treatment of soft tissue sarcoma (STS) of the extremities includes limb-sparing surgery combined with pre- or postoperative radiotherapy (RT). The role of perioperative chemotherapy (CTX) remains uncertain. STS patients with high-risk features for local recurrence, distant metastases, and increased mortality may require additional systemic therapy. The objective of this study was to evaluate predictors of outcome regarding local control (LC), overall survival (OS), and freedom from distant metastases (FFDM) in a large single-center cohort of patients suffering from localized high-grade STS (grade 2/3, G2/G3). Special emphasis was put on a subgroup of patients who received combined neoadjuvant radiochemotherapy (RCT). Methods: Overall, 115 adult STS patients were included in this retrospective study. The median follow-up was 34 months. Twenty-three patients (20.0%) were treated with neoadjuvant RCT, 92 (80.0%) received other therapies (adjuvant RT alone (n = 58); neoadjuvant CTX + adjuvant RT (n = 17); adjuvant RCT (n = 10), neoadjuvant RT alone (n = 7)). To assess potential prognostic factors on LC, OS, and FFDM, univariate (UVA) and multivariable (MVA) Cox proportional hazards models were applied. Results: UVA showed significantly better LC rates in the neoadjuvant RCT group (p = 0.025), with trends in MVA (p = 0.057). The 3-year LC rate was 89.7% in the neoadjuvant RCT group vs. 75.6% in the "other therapies" group. UVA also showed significantly better OS rates in the neoadjuvant RCT group (p = 0.049), however, this was not confirmed in MVA (p = 0.205), the 3-year OS rate was 85.8% for patients treated with neoadjuvant RCT compared to 73.5% in the "other therapies" group. UVA showed significantly better FFDM rates in (p = 0.018) and a trend towards better FFDM rates in MVA (p = 0.059). The 3-year FFDM rate was 89.7% for patients treated with neoadjuvant RCT compared to 65.9% in the "other therapies" group. In the subgroup of patients with G3 STS, neoadjuvant RCT was a significant positive predictor of LC and FFDM in MVA (p = 0.047, p = 0.027) but not for OS. Overall grade 3 and 4 toxicities were significantly higher (p = 0.019) in the neoadjuvant RCT group and occurred in 73.9% vs. 38.0% in patients receiving other therapies. Conclusions: The results suggest that neoadjuvant RCT might improve LC and FFDM in patients with localized G3 STS while also being associated with increased acute complication rates. Further prospective research is warranted to confirm these findings

Empagliflozin reduces the risk of a broad spectrum of heart failure outcomes regardless of heart failure status at baseline

No abstract available