Efficacy of thrombopoietin receptor agonists versus rituximab in non-responsive immune thrombocytopenia-A single centre retrospective analysis

Management of immune thrombocytopenia (ITP) beyond initial glucocorticoid therapy is challenging. In this retrospective single-centre cohort study, we compared all ITP patients relapsed or non-responsive to glucocorticoid therapy treated with either continuous TPO-RAs (n = 35) or rituximab induction (n = 20) between 2015 and 2022. While both groups showed high initial complete response rates (CR, 68.6 vs. 80.0%, ns), the overall rate of progression to the next therapy was higher after time-limited rituximab (75.0 vs. 42.9%), resulting in a lower relapse-free survival (median 16.6 vs. 25.8 months, log-rank; p < 0.05). We conclude that both treatments show similar initial efficacy and their ideal duration of therapy warrants further investigation

Combined Experimental and Theoretical Approach to the Electronic and Magnetic Properties of Cu-Doped LaMnO3 Perovskites

Cu-doped LaCuxMn1–xO3 perovskites have been used as a model system for a joint experimental and theoretical assessment of the influence of the Cu doping level on the structural, electronic, and magnetic properties. The different Cu-doped phases LaCu0.3Mn0.7O3 (LCM37), LaCu0.5Mn0.5O3 (LCM55), and LaCu0.7Mn0.3O3 (LCM73) including the respective Cu- and Mn-free benchmark materials La2CuO4 (LC) and LaMnO3 (LM) have been studied by magnetization measurements and electronic paramagnetic resonance. Ferromagnetic behavior was detected for pure LM and all Cu-doped perovskites, whereas antiferromagnetic behavior was revealed for La2CuO4. Generally, an increased antiferromagnetic contribution was shown for higher Cu doping levels. Equally, magnetization was highlighted to decrease with increasing Cu content. Sophisticated hybrid density functional theory calculations of the electronic and magnetic properties using defect-free, idealized Cu-doped model structures agree well with the experimental results. The findings reveal that copper incorporation influences both the electronic conductivity and the magnetic properties. Notably, the materials exhibit a tunable degree of half-metallicity and significant electronic spin polarization, establishing them as promising candidates for advanced technological applications in spintronics and catalysis. The insights gained from this study contribute to a broader understanding of perovskite materials and their versatile applications

Anesthesia triggers drug delivery to experimental glioma in mice by hijacking caveolar transport

Background Pharmaceutical intervention in the CNS is hampered by the shielding function of the blood–brain barrier (BBB). To induce clinical anesthesia, general anesthetics such as isoflurane readily penetrate the BBB. Here, we investigated whether isoflurane can be utilized for therapeutic drug delivery. Methods Barrier function in primary endothelial cells was evaluated by transepithelial/transendothelial electrical resistance, and nanoscale STED and SRRF microscopy. In mice, BBB permeability was quantified by extravasation of several fluorescent tracers. Mouse models including the GL261 glioma model were evaluated by MRI, immunohistochemistry, electron microscopy, western blot, and expression analysis. Results Isoflurane enhances BBB permeability in a time- and concentration-dependent manner. We demonstrate that, mechanistically, isoflurane disturbs the organization of membrane lipid nanodomains and triggers caveolar transport in brain endothelial cells. BBB tightness re-establishes directly after termination of anesthesia, providing a defined window for drug delivery. In a therapeutic glioblastoma trial in mice, simultaneous exposure to isoflurane and cytotoxic agent improves efficacy of chemotherapy. Conclusions Combination therapy, involving isoflurane-mediated BBB permeation with drug administration has far-reaching the

Incidental findings of borderline ovarian tumor or ovarian cancer – real-world data on surgical and oncological outcomes

IntroductionCentralization of ovarian cancer treatment is associated with higher rates of optimal surgery and longer survival. However, preoperative diagnosis of ovarian cancer is challenging and some diagnoses are made incidentally after surgery. This study investigated the surgical and oncological outcomes of patients with incidental findings of borderline ovarian tumors or ovarian cancer who were centralized postoperatively and treated with a two-stage surgical procedure, and compared these with those of patients with adnexal masses of suspected malignancy who were offered a single-stage surgical procedure with intraoperative frozen section in a tertiary hospital.MethodsA database of 390 patients with adnexal masses and surgical treatment at the Bern University Hospital, Switzerland was retrospectively reviewed to identify patients with borderline ovarian tumors or ovarian cancer between 2010 and 2020.ResultsAmong 390 patients with adnexal masses, 223 were diagnosed with a borderline ovarian tumor or ovarian cancer. Compared with patients with suspected malignancy and a centralized single-stage surgical procedure, patients with an incidental postoperative malignancy diagnosis and a two-stage surgical procedure underwent more surgical interventions (1.3 vs. 2.1 p&lt;.001) and had a longer time interval from diagnosis to initiation of chemotherapy (33.3 vs. 45.1 p=.005) and to completion of surgical cytoreduction (31.9 vs. 73.7 days, p&lt;.001). However, there were no differences in the rates of complete cytoreduction (90.0% vs. 93.2%, p=.719), intraoperative (11.3% vs. 13.7%, p=.664) or postoperative (38.7% vs. 37.0%, p=.884) complication rates, and number of hospitalization days (11.1 vs. 12.0 days, p=.369). An incidental diagnosis of malignancy with postoperative referral was neither associated with an increased risk of recurrence (hazard ratio (HR) 0.8, 95% confidence interval (CI) 0.6-1.8, p=.839) nor death (HR 0.7, 95% CI 0.4-1.1, p=.113), and there was no difference in mean recurrence-free survival between the study subgroups.DiscussionAlthough patients with incidental findings of borderline ovarian tumors or ovarian cancer treated with a two-stage surgical procedure had a longer time to completion of surgical staging and initiation of chemotherapy, our results showed no negative impact on oncological outcomes

Age Differences in Decoding Pain from the Facial Expression of Healthy Individuals and Patients with Dementia

Objective. Patients with dementia, whose ability to provide self-report of pain is often impaired, are in crucial need of observers who can detect the patients' pain-indicative behaviors appropriately, to initiate treatment. The facial display of pain promises to be especially informative for that purpose. The age of the observer has been shown to have a critical influence on observational emotion recognition (with age-related decrements in facial emotion recognition) but has not yet been studied as such for pain recognition. Methods. For that purpose, 24 young (mean age: 24 years) and 22 older (mean age: 70 years) observers watched 120 video clips, showing facial expressions of young and old individuals with and without dementia during slight and moderate noxious stimulation. After each clip, observers were asked to rate how much pain the observed individual might have experienced. Results. Young observers were superior in grading different levels of pain in the observed individuals; furthermore, their ratings corresponded better with the self-ratings of the observed individuals. However, the performance of the older observers was still sufficient as regards the differentiation of different pain levels and prediction of self-report in others. Conclusions. Age does not only lead to a decline in recognition of facial expressions of emotions but age also affects the quality of observational pain recognition in others. However, given that older observers' performance was only slightly reduced, clearly suggests that older caregivers are surely not at risk of becoming visual agnostic for the pain in others

Combined Experimental and Theoretical Approach to the Electronic and Magnetic Properties of Cu Doped LaMnO3 Perovskites

Cu doped LaCuxMn1 amp; 8722;xO3 perovskites have been used as a model system for a joint experimental and theoretical assessment of the influence of the Cu doping level on the structural, electronic, and magnetic properties. The different Cu doped phases LaCu0.3Mn0.7O3 LCM37 , LaCu0.5Mn0.5O3 LCM55 , and LaCu0.7Mn0.3O3 LCM73 including the respective Cu and Mn free benchmark materials La2CuO4 LC and LaMnO3 LM have been studied by magnetization measurements and electronic paramagnetic resonance. Ferromagnetic behavior was detected for pure LM and all Cu doped perovskites, whereas antiferromagnetic behavior was revealed for La2CuO4. Generally, an increased antiferromagnetic contribution was shown for higher Cu doping levels. Equally, magnetization was highlighted to decrease with increasing Cu content. Sophisticated hybrid density functional theory calculations of the electronic and magnetic properties using defect free, idealized Cu doped model structures agree well with the experimental results. The findings reveal that copper incorporation influences both the electronic conductivity and the magnetic properties. Notably, the materials exhibit a tunable degree of half metallicity and significant electronic spin polarization, establishing them as promising candidates for advanced technological applications in spintronics and catalysis. The insights gained from this study contribute to a broader understanding of perovskite materials and their versatile application