A consistent finding of this study was the absence of positive BMBs in PET/CT-assessed stage I to II disease. The omission of staging BMB would not have changed the risk assessment or treatment strategy in this cohort of 454 newly diagnosed patients with HL.
Background and Purpose— Data on long-term outcome after intravenous tissue-type plasminogen activator (tPA) in ischemic stroke are limited. We examined the risk of long-term mortality, recurrent ischemic stroke, and major bleeding, including intracranial and gastrointestinal bleeding, in intravenous tPA-treated patients when compared with intravenous tPA eligible but nontreated patients with ischemic stroke. Methods— We conducted a register-based nationwide propensity score–matched follow-up study among patients with ischemic stroke in Denmark (2004–2011). Cox regression analysis was used to compute adjusted hazard ratios for all outcomes. Results— Among 4292 ischemic strokes (2146 intravenous tPA-treated and 2146 propensity score–matched nonintravenous tPA-treated patients), with a follow-up for a median of 1.4 years, treatment with intravenous tPA was associated with a lower risk of long-term mortality (adjusted hazard ratio, 0.66; 95% confidence interval, 0.49–0.88). The long-term risk of recurrent ischemic stroke (adjusted hazard ratio, 1.05; 95% confidence interval, 0.68–1.64) and major bleeding (adjusted hazard ratio, 0.59; 95% confidence interval, 0.24–1.47) did not differ significantly between the intravenous tPA-treated and nontreated patients. Conclusions— Treatment with intravenous tPA in patients with ischemic stroke was associated with improved long-term survival.
A nucleoside with two nucleobases, a so-called double-headed nucleoside, 5'(S)-C-(thymine-1-ylmethyl)thymidine 3, is synthesised and incorporated into oligonucleotides. The additional nucleobase is hereby positioned in the minor groove of the duplexes, which are formed with complementary DNA and RNA-sequences. Slight thermal destabilisation of these duplexes as compared to unmodified duplexes is observed. With other target sequences forming bulged duplexes or three-way junctions, no additional influence of the additional base on the thermal stability is observed. On the other hand, a base-base stacking interaction and subsequent stabilisation is observed when two double-headed nucleotide moieties are positioned in two complementary DNA-sequences forming a DNA-zipper motif.
PurposeThe purpose of this study is to establish the validity of intracerebral hemorrhage (ICH) diagnoses in the Danish Stroke Registry (DSR) and the Danish National Patient Registry (DNPR).Patients and methodsWe estimated the positive predictive value (PPV) of ICH diagnoses for a sample of 500 patients from the DSR (patients recorded under ICH diagnosis) and DNPR (International Classification of Diseases, version 10, code I61) during 2010–2015, using discharge summaries and brain imaging reports (minimal data). We estimated PPVs for any ICH (a-ICH) and spontaneous ICH (s-ICH) alone. Furthermore, we assessed PPVs according to whether patients were recorded in both or only one of the registries. Finally, in a subsample with ICH diagnoses with access to full medical records and original imaging studies (extensive data, n=100), we compared s-ICH diagnosis and hemorrhage location after use of extensive vs minimal data.ResultsIn the DSR, the PPVs were 94% (95% CI, 91%–96%) for a-ICH and 85% (95% CI, 81%–88%) for s-ICH. In the DNPR, the PPVs were 88% (95% CI, 84%–91%) for a-ICH and 75% (95% CI, 70%–79%) for s-ICH. PPVs for s-ICH for patients recorded in both registries, DSR only, and DNPR only were 86% (95% CI, 82–99), 80% (95%CI, 71–87), and 49% (95%CI, 39–59), respectively. Evaluation of extensive vs minimal data verified s-ICH diagnosis in 98% and hemorrhage location in 94%.ConclusionThe validity of a-ICH diagnoses in DSR and DNPR is sufficiently high to support their use in epidemiologic studies. For s-ICH, validity was high in DSR. In DNPR, s-ICH validity was lower, markedly so for the small subgroup of patients only recorded in this registry. Minimal data including discharge summaries and brain imaging reports were feasible and valid for identifying ICH location.
Background: Ischemic stroke causes increased blood-brain barrier permeability and release of markers of axonal damage and inflammation. To investigate diagnostic and prognostic roles of neurofilament light chain (NF-L), we assessed levels of NF-L, S100B, interleukin-6 (IL-6), E-selectin, vascular endothelial growth factor-A (VEGF-A), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in patients with acute ischemic stroke or transient ischemic attack (TIA) and healthy controls. Methods: We studied neurofilament (NF) expression in 2 cases of human postmortem ischemic stroke, representing infarcts aged 3-to >7-days. In a prospective study, we measured plasma NF-L and inflammatory markers <8 h of symptom onset and at 72 h in acute ischemic stroke (n = 31), TIA (n = 9), and healthy controls (n = 29). We assessed whether NF-L, S100B, and IL-6 were associated with clinical severity on admission (Scandinavian Stroke Scale, SSS), diagnosis of ischemic stroke vs. TIA, and functional outcome at 3 months (modified Rankin Scale, mRS). Results: NF expression increased in ischemic neurons and in the infarcted brain parenchyma after stroke. Plasma NF-L levels were higher in stroke patients than in TIA patients and healthy controls, but IL-6 levels were similar. Higher acute NF-L levels were associated with lower SSS scores at admission and higher mRS scores at 3 months. No correlation was observed between NF-L and S100B, NF-L and IL-6, nor between S100B or IL-6 and SSS or mRS. Compared to controls, stroke patients had significantly higher VEGF-A and VCAM-1 at <8 h that remained elevated at 72 h, with significantly higher VEGF-A at <8 h; ICAM-1 was significantly increased at <8 h, while S100B and E-selectin were unchanged. Nielsen et al. Acute Plasma NF-L Levels in Stroke Conclusions: Plasma NF-L levels, but not IL-6 and S100B, were significant predictors of clinical severity on admission and functional outcome at 3 months. Plasma NF-L is a promising biomarker of functional outcome after ischemic stroke.
Macrocyclic compounds are attractive targets when searching for molecules with biological activity. The interest in this compound class is increasing, which has led to a variety of methods for tackling the difficult macrocyclization step in their synthesis. This microreview highlights some recent developments in the synthesis of macrocycles, with an emphasis on chemistry developed to generate libraries of putative biologically active compounds.
Purpose: To establish the validity of intracerebral hemorrhage (ICH) diagnoses in the Danish Stroke Registry (DSR) and the Danish National Patient Registry (DNPR). Patients and Methods: Based on discharge summaries and brain imaging reports, we estimated the positive predictive value (PPV) of a first-ever diagnosis code for ICH (ICD-10, code I61) for all patients in the Region of Southern Denmark (1.2 million) during 2009-2017 according to either DNPR or DSR. We estimated PPVs for any non-traumatic ICH (a-ICH) and spontaneous ICH (s-ICH) alone (ie, without underlying structural cause). We also calculated the sensitivity of these diagnoses in each of the registers. Finally, we classified the location of verified s-ICH. Results: A total of 3,956 patients with ICH diagnosis codes were studied (DSR only: 87; DNPR only: 1,513; both registries: 2,356). In the DSR, the PPVs were 86.5% (95% CI=85.1-87.8) for a-ICH and 81.8% (95% CI=80.2-83.3) for s-ICH. The PPVs in DNPR (discharge code, primary diagnostic position) were 76.2% (95% CI=74.7-77.6) for a-ICH and 70.2% (95% CI=68.6-71.8) for s-ICH. Sensitivity for a-ICH and s-ICH was 76.4% (95% CI=74.8-78.0) and 78.7% (95% CI=77.1-80.2) in DSR, and 87.3% (95% CI=86.0-88.5) and 87.7% (95% CI=86.3-88.9) in DNPR. The location of verified s-ICH was lobar (39%), deep (33.6%), infratentorial (13.2%), large unclassifiable (11%), isolated intraventricular (1.9%), or unclassifiable due to insufficient information (1.3%). Conclusion: The validity of a-ICH diagnoses is high in both registries. For s-ICH, PPV was higher in DSR, while sensitivity was higher in DNPR. The location of s-ICH was similar to distributions seen in other populations.
Structure from Motion 3D reconstruction has become widely used in recent years in a number of fields such as industrial surface inspection, archeology, cultural heritage preservation and geomapping. A number of software solutions have been released using variations of this technique. In this paper we analyse the state of the art of these software applications, by comparing the resultant 3D meshes qualitatively and quantitatively. We propose a number of testing scenarios using different lighting conditions, camera positions and image acquisition methods for the best in-depth analysis and discuss the results, the overall performance and the problems present in each software. We employ distance and roughness metrics for evaluating the final reconstruction results.
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