In vivo quantification of photosensitizer fluorescence in the skin-fold observation chamber using dual-wavelength excitation and NIR imaging

A major challenge in biomedical optics is the accurate quantification of in vivo fluorescence images. Fluorescence imaging is often used to determine the pharmacokinetics of photosensitizers used for photodynamic therapy. Often, however, this type of imaging does not take into account differences in and changes to tissue volume and optical properties of the tissue under interrogation. To address this problem, a ratiometric quantification method was developed and applied to monitor photosensitizer meso-tetra (hydroxyphenyl) chlorin (mTHPC) pharmacokinetics in the rat skin-fold observation chamber. The method employs a combination of dual-wavelength excitation and dualwavelength detection. Excitation and detection wavelengths were selected in the NIR region. One excitation wavelength was chosen to be at the Q band of mTHPC, whereas the second excitation wavelength was close to its absorption minimum. Two fluorescence emission bands were used; one at the secondary fluorescence maximum of mTHPC centered on 720 nm, and one in a region of tissue autofluorescence. The first excitation wavelength was used to excite the mTHPC and autofluorescence and the second to excite only autofluorescence, so that this could be subtracted. Subsequently, the autofluorescence-corrected mTHPC image was divided by the autofluorescence signal to correct for variations in tissue optical properties. This correction algorithm in principle results in a linear relation between the corrected fluorescence and photosensitizer concentration. The limitations of the presented method and comparison with previously published and validated techniques are discussed

Prevention of infections and fever to improve outcome in older patients with acute stroke (PRECIOUS): a randomised, open, phase III, multifactorial, clinical trial with blinded outcome assessment

BackgroundInfections and fever after stroke are associated with poor functional outcome or death. We assessed whether prophylactic treatment with anti-emetic, antibiotic, or antipyretic medication would improve functional outcome in older patients with acute stroke. MethodsWe conducted an international, 2∗2∗2-factorial, randomised, controlled, open-label trial with blinded outcome assessment in patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and a score on the National Institutes of Health Stroke Scale ≥ 6. Patients were randomly allocated (1:1) to metoclopramide (oral, rectal, or intravenous; 10 mg thrice daily) vs. no metoclopramide, ceftriaxone (intravenous; 2000 mg once daily) vs. no ceftriaxone, and paracetamol (oral, rectal, or intravenous; 1000 mg four times daily) vs. no paracetamol, started within 24 h after symptom onset and continued for four days. All participants received standard of care. The target sample size was 3800 patients. The primary outcome was the score on the modified Rankin Scale (mRS) at 90 days analysed with ordinal logistic regression and reported as an adjusted common odds ratio (an acOR 1 harm). This trial is registered (ISRCTN82217627). FindingsFrom April 2016 through June 2022, 1493 patients from 67 European sites were randomised to metoclopramide (n = 704) or no metoclopramide (n = 709), ceftriaxone (n = 594) or no ceftriaxone (n = 482), and paracetamol (n = 706) or no paracetamol (n = 739), of whom 1471 were included in the intention-to-treat analysis. Prophylactic use of study medication did not significantly alter the primary outcome at 90 days: metoclopramide vs. no metoclopramide (adjusted common odds ratio [acOR], 1.01; 95% CI 0.81–1.25), ceftriaxone vs. no ceftriaxone (acOR 0.99; 95% CI 0.77–1.27), paracetamol vs. no paracetamol (acOR 1.19; 95% CI 0.96–1.47). The study drugs were safe and not associated with an increased incidence of serious adverse events. InterpretationWe observed no sign of benefit of prophylactic use of metoclopramide, ceftriaxone, or paracetamol during four days in older patients with a moderately severe to severe acute stroke. FundingThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No: 634809

Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

Introduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. Methods: For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland–Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. Results: The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Conclusion: Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs

Acute Endovascular Treatment of Patients With lschemic Stroke From Intracranial Large Vessel Occlusion and Extracranial Carotid Dissection

Introduction: Carotid artery dissection (CAD) and atherosclerotic carotid artery occlusion (ACAO) are major causes of a tandem occlusion in patients with intracranial large vessel occlusion (LVO). Presence of tandem occlusions may hamper intracranial access and potentially increases the risk of procedural complications of endovascular treatment (EVT). Our aim was to assess neurological, functional and technical outcome and complications of EVT for intracranial LVO in patients with CAD in comparison to patients with ACAO and to patients without CAD or ACAO. Methods: We analyzed data of the MR CLEAN trial intervention arm and MR CLEAN Registry, acquired in 16 Dutch EVT-centers. Primary outcome was the change in stroke severity by comparing the National Institute of Health Stroke Scale (NIHSS) score at 24-48 h after treatment vs. baseline. Secondary outcomes included reperfusion rate and symptomatic intracranial hemorrhage (sICH). We compared outcomes and complications between patients with CAD vs. patients with ACAO and patients without CAD or ACAO. Results: In total, we identified 74 (4.7%) patients with CAD, 92 (5.9%) patients with ACAO and 1398 (89.4%) patients without CAD or ACAO. Neurological improvement at short-term after EVT in patients with CAD was significantly better compared to ACAO (raw mean -5 vs. mean -1 NIHSS point; p = 0.03) and did not differ compared to patients without CAD or ACAO (-4 NIHSS points; p = 0.62). Rates of successful reperfusion in patients with CAD (47%) was comparable to patients with ACAO (47%; p = 1.00), but was less often achieved compared to patients without CAD or ACAO (58%; p = 0.08). Occurrence of sICH did not differ significantly between CAD patients (5%) and ACAO (11%; p = 0.33) or without CAD/ACAO (6%; p = 1.00). Conclusion: EVT in patients with intracranial LVO due to CAD results in neurological improvement comparable to patients without tandem occlusions. Therefore, carotid artery dissection by itself should not be a contraindication for endovascular treatment in stroke patients with intracranial large vessel occlusion. Although more challenging endovascular procedures are to be suspected in both patients with CAD or ACAO, accurate distinction between CAD and ACAO might influence clinical decision making as better clinical outcome can be expected in patients with CAD

Bell's palsy:a broad differential diagnosisHouse-Brackmann-schaal

Peripheral facial palsy is a common clinical symptom and is most often caused by Bell's palsy. The pathogenesis is largely unknown, but inflammation of the facial nerve, possibly after a viral infection, may play a role. Bell's palsy has a monophasic course with usually - but not always - a good recovery. Even though Bell's palsy exhibits clear clinical features, in clinical practice diagnosis and choice of treatment remain difficult and other causes of an isolated facial palsy may easily be overlooked. Score INormale functie van aangezicht op alle gebieden Score II Globaal: lichte zwakte bij nauwkeurig onderzoek; mogelijk zeer lichte synkinesieën. In rust: normale symmetrie en tonus. Motoriek: - Voorhoofd: matig tot goede functie. - Oog: volledige sluiting met minimale inspanning. - Mond: lichte asymmetrie. Score IIIGlobaal: duidelijke, maar niet-ontsierend verschil tussen twee zijdes; opvallende, maar geen ernstige synkinesieën, contracturen of hemifacialisspasmen. In rust: normale symmetrie en tonus. Motoriek: - Voorhoofd: lichte tot matige beweging. - Oog: volledige sluiting met inspanning. - Mond: lichte zwakte met maximale inspanning. Score IV Globaal: duidelijke zwakte of ontsierende asymmetrie. In rust: normale symmetrie en tonus. Motoriek: - Voorhoofd: geen. - Oog: onvolledige sluiting. - Mond: asymmetrie met maximale inspanning. Score V Globaal: nauwelijks waarneembare beweging. In rust: asymmetrie. Motoriek: - Voorhoofd: geen. - Oog: onvolledige sluiting. - Mond: lichte beweging. Score VI Geen beweging.</p

Conceptions of sleep experience: a layman perspective

Abstract Objective To date, there is little information on how lay people understand and discuss sleep in the context of daily life. Efforts to conceptualize sleep quality have been largely driven by clinical considerations of sleep disorders. As such, they are not necessarily of how normal sleepers without clinical expertise conceptualize sleep quality. A phenomenological approach was taken to understand the essence of the sleep experience and the concepts held by lay people without sleep disorders. A sentence completion questionnaire was developed and administered to a quota sample of 64 respondents who were selected aiming for sufficient representation of different gender, ages, and education levels. Results Significant sentences and meaningful units were derived inductively, resulting in a classification of nine categories. The major facets of sleep experience of lay people were ‘daytime functioning’, ‘interruptions during the night’ and ‘before bed state’. This implies that the experienced sleep quality is not only depending on the progress of the night. These results can guide future research to provide suitable psychometric measures for normal sleepers, as well as the design of sleep data visualization applications in the context of health self-monitoring