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Background and purpose: Acute ischemic stroke treatment with intravenous thrombolysis (IVT) is restricted to a time window of 4.5 h after known or presumed onset. Recently, magnetic resonance imaging‐guided treatment decision‐making in wake‐up stroke (WUS) was shown to be effective. The aim of this study was to determine the safety and outcome of IVT in patients with a time window beyond 4.5 h selected by computed tomography perfusion (CTP) imaging. Methods: We analyzed all consecutive patients last seen well beyond 4.5 h after stroke onset treated with IVT based on CTP between January 2015 and October 2018. CTP was visually assessed to estimate the mismatch between cerebral blood flow and cerebral blood volume maps. Early infarct signs were documented according to Alberta Stroke Program Early CT Score (ASPECTS). Safety data were obtained for mortality and symptomatic intracerebral hemorrhage (sICH). Follow‐up was assessed with the modified Rankin Scale (mRS). Results: A total of 70 patients fulfilled the inclusion criteria (mean age ± SD 77.6 ± 11.5 years, 50.0% female). Median National Institutes of Health Stroke Scale score on admission was 8.0 [interquartile range (IQR), 4–14]. The most frequent reasons for an extended time window were WUS (60.0%) and delayed hospital admission (27.1%). Median time from last seen well to IVT was 11.4 h. Median ASPECTS was 10 (IQR, 9–10) and CTP mismatch 90% (IQR, 80%–100%). A total of 24 patients (34.3%) underwent additional mechanical thrombectomy. sICH occurred in four patients (5.7%). At follow‐up, 49.3% had an mRS score of 0–2 and 22.4% had an mRS score of 0–1. Conclusions: In patients presenting in an extended time window beyond 4.5 h, IVT treatment with decision‐making based on CTP might be a safe procedure. Further evaluation in clinical trials is needed. [ABSTRACT FROM AUTHOR]

Background: Management of intracerebral hemorrhage (ICH) is challenged by limited therapeutic options and a complex relationship between blood pressure (BP) dynamics, especially BP variability (BPV) and ICH outcome., Methods: In an exploratory analysis of prospectively collected data on consecutive patients with nontraumatic ICH between 2015 and 2020, continuous BP accessed via an arterial line extracted from the Intellispace Critical Care and Anesthesia information system (Philips Healthcare) was analyzed over the first 72 h post admission. Arterial lines were used as part of standard clinical practice in the intensive care, ensuring high fidelity and real-time data essential for acute care settings. BPV was assessed through successive variation (SV), standard deviation (SD), and coefficient of variation using all available BP measurements. Multivariate regression models were applied to evaluate the association between BPV indices and functional outcome at 3 months., Results: Among 261 patients (mean age 69.6 ± 15.2 years, 47.9% female, median National Institutes of Health Stroke Scale [NIHSS] score 6 [interquartile range 2-12]) analyzed, lower systolic BP upon admission (< 140 mm Hg) and lower systolic BPV were significantly associated with favorable outcome, whereas higher diastolic BPV correlated with improved outcomes. In the multivariate analysis, diastolic BPV (SD, SV) within the first 72 h post admission emerged as an independent predictor of good functional outcome (modified Rankin Scale score < 3; odds ratio 1.123, 95% confidence interval CI 1.008-1.184, p = 0.035), whereas systolic BPV (SD) showed a negative association. Patients with better outcomes also exhibited distinct clinical characteristics, including younger age, lower median NIHSS scores, and less prevalence of anticoagulation therapy upon admission., Conclusions: This study shows the prognostic value of BPV in the acute phase of ICH. Lower systolic BPV (SD) and higher diastolic BPV (SD, SV) were associated with better functional outcomes, challenging traditional BP management strategies. These findings might help to tailor a personalized BP management in ICH., (© 2024. The Author(s).)

Rhino-orbital-cerebral mucormycosis is a rapidly progressive and often fatal fungal infection caused by molds of the order Mucorales , particularly affecting immunocompromised individuals. This infection is notorious for its angioinvasive properties, enabling the fungi to invade blood vessels and leading to tissue necrosis. We report the clinical course of a 59-year-old Caucasian man with poorly controlled type 2 diabetes (HbA1c 16.8%) who presented with unilateral headache, left-sided facial numbness, and incomplete left ocular motor paresis. Initial presentation raised suspicion of orbital phlegmon, leading to antibiotic and later corticosteroid pulse therapy, which worsened the patient's condition. Subsequent imaging demonstrated extensive inflammatory changes, including wall irregularities of the left intracranial internal carotid artery, accompanied by ocular protrusion and periorbital enhancement. New palatal lesions indicated mucormycosis, which was confirmed by molecular analysis of a palatal biopsy, leading to Amphotericin B treatment. Pre-surgery imaging revealed a malignant middle cerebral artery infarction, and the patient died 16 days after symptom onset and 12 days after initial presentation under palliative care due to a poor prognosis. This case of angioinvasive mucormycosis underscores the severe and often fatal course of rhino-orbital-cerebral mucormycosis in an immunocompromised individual. The rapid progression from initially vague and unspecific symptoms to extensive vascular involvement and stroke highlights the critical need for early and accurate diagnosis, as well as prompt intervention to prevent further disease progression. Additionally, this case also illustrates the potential risks associated with corticosteroid therapy in the presence of undiagnosed fungal infections, which can exacerbate the condition and lead to serious complications. Clinicians should maintain a high index of suspicion for mucormycosis in similar clinical scenarios, prioritizing adequate antifungal treatment and careful monitoring to improve patient outcomes. Early interdisciplinary collaboration is essential for the effective management of such complex cases., Competing Interests: The authors declare no conflicts of interest.

The vaginal microbiome of trans men and menopausal women is suspected to be similar due to a lack of estrogen leading to the absence of lactobacilli. However, data are scarce. We performed an analysis of the vaginal microbiome of trans men (n = 25) in comparison to that of menopausal (n = 25) and premenopausal women (n = 25). The vaginal microbiome of trans men and menopausal women showed a higher alpha diversity than that of premenopausal women. Various beta diversity indices (e.g., Bray‒Curtis (Un-)Weigthed Unifrac), showed significant differences in community composition between trans men and premenopausal (p < 0.001) and menopausal women (p < 0.001). The vaginal microbiome of trans men is characterized by a loss of Lactobacillus and an increase in bacteria associated with the intestinal flora (e.g., Campylobacter, Anaerococcus, Dialister, Prevotella). The abundance of Dialister and Prevotella decreased with the length of hormonal therapy in trans men. The Nugent score, Pap smear and HPV status did not differ between the study groups. The vaginal microbiome of trans men differs from that of premenopausal women but shows similarities to that of menopausal women. The duration of hormonal therapy in trans men may have important impacts on the vaginal microbiome and thus possibly on the risk for STIs., (© 2024. The Author(s).)

Introduction: Akinetic crisis is a severe deterioration of motor performance occurring in syndromes with pre- or postsynaptic dopaminergic deficit, necessitating effective dopamine replacement therapy. The subcutaneously applicable levodopa derivative foslevodopa represents a new therapeutic option for patients with advanced Parkinson's disease as a continuous therapy. However, its potential role as a parenteral treatment option for akinetic crisis has not been investigated, yet., The Case: A 78 year-old patient who had developed akinetic-rigid symptomatology in the context of normal pressure hydrocephalus was admitted to our intensive care unit after experiencing an acute exacerbation of akinesia in the context of pulmonary infection. Off-label administration of subcutaneous foslevodopa was initiated after repeated failures to insert a gastric tube for enteral application of levodopa and contraindications against amantadine and apomorphine., Results: Following the administration of a subcutaneous test dose, continuous application of foslevodopa via a B. Braun syringe pump was gradually increased to 0.3 mL/h during the daytime and 0.15 mL/h at night, corresponding to a levodopa equivalent dosage of 1,020 mg/d. This was accompanied by an improvement of the MDS-UPDRS III score from 85 points to 59 points after 72 h., Discussion: Treatment of an akinetic crisis with subcutaneous foslevodopa in an intensive care unit setting has proven to be safe and effective in a patient with acute akinesia associated with dopamine-sensitive hydrocephalus. Due to the pathophysiological distinction from Parkinson's disease, there may be differences in therapeutic response and side effects. Nevertheless, the method used here can serve as a protocol basis for the treatment of akinetic crises with foslevodopa in general and as a starting point for further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Loeffler, Mengel, Single, Weiss and Feil.)

Background: The relationship between heart rate variability (HRV) changes potentially indicating autonomic dysregulation following spontaneous intracerebral hemorrhage (ICH) and functional outcome has not yet been fully elucidated. This study investigated the effects of HRV during the initial 96 h after admission on 90-day functional outcome in ICH patients., Methods: We included patients with spontaneous ICH in a prospective cohort single-center study. Continuous HR data were retrieved from the Intellispace Critical Care and Anesthesia information system (Philips Healthcare) and analyzed within the following time intervals: 0-2, 0-8, 0-12, 0-24, 0-48, 0-72, and 8-16, 16-24, 24-48, 48-72, 72-96 h after admission. HRV was determined from all available HR values by calculating the successive variability (SV), standard deviation (SD), and coefficient of variation (CV). Low HRV was set as SD ≤ 11.4 ms, and high HRV as SD > 11.4 ms. The clinical severity of ICH was assessed using the National Institutes of Health Stroke Scale (NIHSS) and functional outcome using the modified Rankin Scale (mRS). Good functional outcome was defined as mRS 0-2., Results: The cohort included 261 ICH patients (mean age ± SD 69.6 ± 16.5 years, 48.7% female, median NIHSS 6 (2, 12), median ICH score 1 (0, 2), of whom 106 (40.6%) had good functional outcome. All patients had the lowest HRV at admission, which increased during the first two days. Comparing ICH patients with low HRV (n = 141) and high HRV (n = 118), those with good outcome showed significantly lower HRV during the first three days (0-72 h: HRV SD good outcome 10.6 ± 3.5 ms vs. poor outcome 12.0 ± 4.0 ms; p = 0.004). Logistic regression revealed that advanced age, high premorbid mRS, and high NIHSS at admission were significant predictors of poor functional outcome, while reduced SD of HRV showed a non-significant trend towards good functional outcome (0-72 h: OR 0.898; CI 0.800-1.008; p = 0.067)., Conclusions: Our results indicate autonomic dysfunction with sympathetic hyperactivity after spontaneous ICH, as reflected by the evidence of the lower HRV in the first days. Initially increased sympathetic tone appears to have a protective effect, as suggested by the comparatively lower HRV in patients with good functional outcome at the first days., Competing Interests: Kornelia Laichinger reports no conflict of interest. Annerose Mengel received grants from the University of T&uuml;bingen (AKF) and speakers&rsquo; honoraria/consulting fees from AMGEN, all not related to this work. Rebecca Buesink reports no conflict of interest. Sara Roesch reports no conflict of interest. Maria-Ioanna Stefanou reports no conflict of interest. Constanze Single reports no conflict of interest. Till-Karsten Hauser reports no conflict of interest. Markus Krumbholz reports no conflict of interest. Ulf Ziemann received grants from the European Research Council (ERC), German Ministry of Education and Research (BMBF), German Research Foundation (DFG), Else-Kr&ouml;ner Fresenius Foundation, and consulting fees from CorTec GmbH, all not related to this work. Katharina Feil received grants from the University of T&uuml;bingen (AKF) and speakers&rsquo; honoraria/consulting fees from AstraZeneca and BMS/Pfizer, all not related to this work.

The integration of digital interventions in health rehabilitation offers promising opportunities to improve patient outcomes. However, empirical studies comparing the effectiveness of digital and traditional rehabilitation interventions remain scarce. This study was designed to evaluate the impact of a digital aftercare program, compared to traditional aftercare and a control group, on both psychological and physical health outcomes in individuals undergoing orthopedic rehabilitation. Additionally, the study also aimed to examine the moderating effects of age and gender. The study employed a partially controlled trial design, engaging a cohort of 805 orthopedic patients, divided into: digIRENA ( n  = 323, digital aftercare), IRENA ( n  = 252, traditional aftercare), and a control group ( n  = 230, without organized aftercare). Measurements took place at four different time points: baseline (start of the rehabilitation program), T1 (13 weeks after the start of rehabilitation, marking the midpoint of aftercare), T2 (26 weeks, marking the end of aftercare), and T3 (43 weeks, to assess the sustainability of aftercare effects). The SF-12 Health Survey was the primary data collection instrument for measuring trends in physical and mental health outcomes over these intervals using repeated measures ANOVA. The results show that rehabilitants in the digIRENA group participated for a longer period of time than rehabilitants in the IRENA group, while the two groups did not differ in terms of motivation at T0 and organized physical activity outside of aftercare at T3. A significant improvement in physical health outcomes was observed in all groups across time, with digIRENA participants showing the greatest improvement. For mental health, all groups showed initial improvements, with the digIRENA group showing the most pronounced increase at T2. Overall, there was a decline in the effects achieved 4 months after the end of aftercare. When age and gender were included as covariates, the time effect for mental health disappeared, showing a significant time * gender interaction due to significantly lower baseline scores of women compared to men. The results of the study show that digital interventions, in particular the digIRENA program, contribute to improving health rehabilitation outcomes. The digIRENA program and similar digital health interventions may offer potential for improving health rehabilitation aftercare., Competing Interests: In the interest of full disclosure and maintaining the integrity of this study, it is important to acknowledge that two of our team members, DS and L-MR, are employed by Knappschaft-Bahn-See, a branch of the Deutsche Rentenversicherung. This association may present a potential conflict of interest due to the organization’s direct involvement in the realm of health rehabilitation and insurance. However, we affirm that the analysis, interpretations, and conclusions drawn in this study have been conducted with the utmost objectivity and are based solely on the data collected and the rigorous methodologies employed. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Schmidt, Fritsch, Feil, Weyland, Rittmann and Jekauc.)

Competing Interests: Katharina Feil erhält eine Förderung von Böhringer Ingelheim (LEXI-Studie), AKF-Förderung (ANNES) der Eberhard-Karls-Universität Tübingen und Vortragshonorare von Pfizer. Tim W. Rattay hat keine Interessenkonflikte und keine laufende Drittmittelförderung. Adedolapo Kamaldeen Adeyemi hat keine Interessenkonflikte und keine laufende Drittmittelförderung. Nicolina Goldschagg hat keine Interessenkonflikte. Michael Strupp is Joint Chief Editor of the Journal of Neurology, Editor in Chief of Frontiers of Neuro-otology and Section Editor of F1000. He has received speaker’s honoraria from Abbott, Auris Medical, Biogen, Eisai, Grünenthal, GSK, Henning Pharma, Interacoustics, J & J, MSD, NeuroUpdate, Otometrics, Pierre-Fabre, TEVA, UCB, and Viatris. He receives support for clinical studies from Decibel, U. S. A., Cure within Reach, U. S. A. and Heel, Germany. He distributes “M-glasses” and “Positional vertigo App”. He is an investor and share-holder of IntraBio. He acts as a consultant for Abbott, AurisMedical, Bulbitec, Heel, IntraBio, Sensorion and Vertify.