Background and Purpose To provide real-world data on outcome and procedural factors of late thrombectomy patients. Methods We retrospectively analyzed patients from the multicenter German Stroke Registry. The primary endpoint was clinical outcome on the modified Rankin scale (mRS) at 3 months. Trial-eligible patients and the subgroups were compared to the ineligible group. Secondary analyses included multivariate logistic regression to identify predictors of good outcome (mRS ≤ 2). Results Of 1917 patients who underwent thrombectomy, 208 (11%) were treated within a time window ≥ 6–24 h and met the baseline trial criteria. Of these, 27 patients (13%) were eligible for DAWN and 39 (19%) for DEFUSE3 and 156 patients were not eligible for DAWN or DEFUSE3 (75%), mainly because there was no perfusion imaging (62%; n = 129). Good outcome was not significantly higher in trial-ineligible (27%) than in trial-eligible (20%) patients (p = 0.343). Patients with large trial-ineligible CT perfusion imaging (CTP) lesions had significantly more hemorrhagic complications (33%) as well as unfavorable outcomes. Conclusion In clinical practice, the high number of patients with a good clinical outcome after endovascular therapy ≥ 6–24 h as in DAWN/DEFUSE3 could not be achieved. Similar outcomes are seen in patients selected for EVT ≥ 6 h based on factors other than CTP. Patients triaged without CTP showed trends for shorter arrival to reperfusion times and higher rates of independence.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients’ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers' burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients' CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patients' functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King’s Stages for ALS. The caregivers' burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregivers' burden was high (mean ZBI = 26/88, 0 = no burden, ≥24 = highly burdened) and correlated with patients' functional status (r\(_p\) = −0.555, p < 0.001, n = 242). It was influenced by the CGs' own mental health issues due to caregiving (+11.36, 95% CI [6.84; 15.87], p < 0.001), patients' wheelchair dependency (+9.30, 95% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs' depression (r\(_p\) = 0.627, p < 0.001, n = 234), anxiety (r\(_p\) = 0.550, p < 0.001, n = 234), and poorer physical condition (r\(_p\) = −0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients' impairment in daily routine (r\(_s\) = −0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGs' lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGs' work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required.

The reassessment of known but neglected natural compounds is a vital strategy for providing novel lead structures urgently needed to overcome antimicrobial resistance. Scaffolds with resistance-breaking properties represent the most promising candidates for a successful translation into future therapeutics. Our study focuses on chelocardin, a member of the atypical tetracyclines, and its bioengineered derivative amidochelocardin, both showing broad-spectrum antibacterial activity within the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) panel. Further lead development of chelocardins requires extensive biological and chemical profiling to achieve favorable pharmaceutical properties and efficacy. This study shows that both molecules possess resistance-breaking properties enabling the escape from most common tetracycline resistance mechanisms. Further, we show that these compounds are potent candidates for treatment of urinary tract infections due to their in vitro activity against a large panel of multidrug-resistant uropathogenic clinical isolates. In addition, the mechanism of resistance to natural chelocardin was identified as relying on efflux processes, both in the chelocardin producer Amycolatopsis sulphurea and in the pathogen Klebsiella pneumoniae. Resistance development in Klebsiella led primarily to mutations in ramR, causing increased expression of the acrAB-tolC efflux pump. Most importantly, amidochelocardin overcomes this resistance mechanism, revealing not only the improved activity profile but also superior resistance-breaking properties of this novel antibacterial compound.

Background: We present a descriptive and retrospective analysis of revision total hip arthroplasties (THA) using the MRP-TITAN stem (Peter Brehm, Weisendorf, GER) with distal diaphyseal fixation and metaphyseal defect augmentation. Our hypothesis was that the metaphyseal defect augmentation (Impaction Bone Grafting) improves the stem survival. Methods: We retrospectively analyzed the aggregated and anonymized data of 243 femoral stem revisions. 68 patients with 70 implants (28.8%) received an allograft augmentation for metaphyseal defects; 165 patients with 173 implants (71.2%) did not, and served as controls. The mean follow-up was 4.4 +/- 1.8 years (range, 2.1-9.6 years). There were no significant differences (p > 0.05) between the study and control group regarding age, body mass index (BMI), femoral defects (types I-III as described by Paprosky), and preoperative Harris Hip Score (HHS). Postoperative clinical function was evaluated using the HHS. Postoperative radiologic examination evaluated implant stability, axial implant migration, signs of implant loosening, periprosthetic radiolucencies, as well as bone regeneration and resorption. Results: There were comparable rates of intraoperative and postoperative complications in the study and control groups (p > 0.05). Clinical function, expressed as the increase in the postoperative HHS over the preoperative score, showed significantly greater improvement in the group with Impaction Bone Grafting (35.6 +/- 14.3 vs. 30.8 +/- 15.8; p <= 0.05). The study group showed better outcome especially for larger defects (types II C and III as described by Paprosky) and stem diameters >= 17 mm. The two groups did not show significant differences in the rate of aseptic loosening (1.4% vs. 2.9%) and the rate of revisions (8.6% vs. 11%). The Kaplan-Meier survival for the MRP-TITAN stem in both groups together was 93.8% after 8.8 years. [Study group 95.7% after 8.54 years; control group 93.1% after 8.7 years]. Radiologic evaluation showed no significant change in axial implant migration (4.3% vs. 9.3%; p = 0.19) but a significant reduction in proximal stress shielding (5.7% vs. 17.9%; p < 0.05) in the study group. Periprosthetic radiolucencies were detected in 5.7% of the study group and in 9.8% of the control group (p = 0.30). Radiolucencies in the proximal zones 1 and 7 according to Gruen occurred significantly more often in the control group without allograft augmentation (p = 0.05). Conclusion: We present the largest analysis of the impaction grafting technique in combination with cementless distal diaphyseal stem fixation published so far. Our data provides initial evidence of improved bone regeneration after graft augmentation of metaphyseal bone defects. The data suggests that proximal metaphyseal graft augmentation is beneficial for large metaphyseal bone defects (Paprosky types IIC and III) and stem diameters of 17 mm and above. Due to the limitations of a retrospective and descriptive study the level of evidence remains low and prospective trials should be conducted.

Es wurde eine Vielzahl neuer, flüssigkristalliner Phthalocyanin-Sternmesogene synthetisiert. Die Struktur-Eigenschaftsbeziehungen und die thermotropen Eigenschaften neuer Phthalocyanin-Sternmesogene mit Freiraum sowie von sterisch überfrachteten Verbindungen wurden insbesondere hinsichtlich der Freiraumfüllung untersucht. Diesbezüglich wurde ein neuer supramolekularer, freiraumfüllender "Klick-Prozess" zwischen einem Molekül mit Freiraum und einem sterisch überfrachteten Molekül mit vier Fullerenen beobachtet. Die photophysikalischen Eigenschaften wurden zudem insbesondere im Hinblick auf die Anwendung für die Organische Photovoltaik untersucht.