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AIM: The aim of this study was to re-evaluate risk factors for post-ICH epilepsy (PICHE) and examine the impact of surgical hematoma evacuation on epilepsy development after ICH. BACKGROUND AND PURPOSE: Epilepsy is a common complication after intracerebral hemorrhage (ICH). Information on risk factors is still scarce and the role of ICH evacuation remains uncertain. METHODS: We retrospectively included patients with spontaneous ICH treated in our hospital in 2006-2019. Patients' medical records were analyzed. In addition, mailed questionnaires and telephone interviews were used to complete the dataset. Uni- and multivariable hazard ratios (HRs) were applied to investigate risk factors for PICHE and the impact of surgical ICH evacuation. RESULTS: Among 587 ICH patients available for analyses, 139 (23.7%) developed PICHE (mean follow-up 1795 ± 1378 days). The median time of epilepsy onset was 7 months after ICH (range 1-132 months). Risk factors associated with PICHE were cortical hemorrhage (multivariable HR 1.65 [95% CI 1.14-2.37]; p = 0.008), ICH volume > 10 ml (multivariable HR 1.91 [95% CI 1.33-2.73]; p < 0.001) and acute symptomatic seizures (multivariable HR 1.81 [95% CI 1.20-2.75]; p = 0.005). Patients with cortical ICH > 10 ml who underwent surgical hematoma evacuation were less likely to develop epilepsy than those with conservative treatment alone (multivariable HR 0.26 [95% CI 0.08-0.84]; p = 0.025). CONCLUSIONS: Post-ICH epilepsy is frequent and predicted by large cortical ICH and acute symptomatic seizures. Hematoma evacuation reduced the risk of PICHE by more than 70% in patients with large cortical ICH. This finding could be considered in the clinical decision making on the acute treatment of ICH.
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Hemorragia Cerebral , Epilepsia , Humanos , Estudios Retrospectivos , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/cirugía , Hematoma/etiología , Hematoma/cirugía , Convulsiones/complicaciones , Epilepsia/cirugía , Epilepsia/complicaciones , Resultado del TratamientoRESUMEN
PURPOSE: Recent studies postulate a high prognostic value of the Alberta Stroke Programme Early CT Score (ASPECTS) applied on non-contrast whole-brain flat-detector CT (FDCT) after successful endovascular treatment (EVT). The aim of this study was the evaluation of long-term patient outcome after endovascular treatment using postinterventional FDCT. METHODS: Using a local database (Stroke Research Consortium in Northern Bavaria, STAMINA), 517 patients with successful endovascular treatment (modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2B) due to acute ischaemic stroke (AIS) and large vessel occlusion (LVO) of the anterior circulation were recruited retrospectively. In all cases, non-contrast FDCT after EVT was analysed with special focus at ASPECTS. These results were correlated with the functional outcome in long-term (modified Rankin Scale (mRS) shift from pre-stroke to 90 days after discharge). RESULTS: A significant difference in FDCT-ASPECTS compared to the subgroup of favourable vs. unfavourable outcome (Δ mRS) (median ASPECTS 10 (10-9) vs. median ASPECTS 9 (10-7); p = 0,001) could be demonstrated. Multivariable regression analysis revealed FDCT-ASPECTS (OR 0.234, 95% CI - 0.102-0.008, p = 0.022) along with the NHISS at admission (OR 0.169, 95% CI 0.003-0.018, p = 0.008) as independent factors for a favourable outcome. Cut-off point for a favourable outcome (Δ mRS) was identified at an ASPECTS ≥ 8 (sensitivity 90.6%, specificity 35%). CONCLUSION: For patients with LVO and successful EVT, FDCT-ASPECTS was found to be highly reliable in predicting long-term outcome.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Alberta , Estudios Retrospectivos , Procedimientos Endovasculares/efectos adversos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Trombectomía/efectos adversosRESUMEN
BACKGROUND: Several automated computed tomography perfusion software applications have been developed to provide support in the definition of ischemic core and penumbra in acute ischemic stroke. However, the degree of interchangeability between software packages is not yet clear. Our study aimed to evaluate 2 commonly used automated perfusion software applications (Syngo.via and RAPID) for the indication of ischemic core with respect to the follow-up infarct volume (FIV) after successful recanalization and with consideration of the clinical impact. METHODS: Retrospectively, 154 patients with large vessel occlusion of the middle cerebral artery or the internal carotid artery, who underwent endovascular therapy with a consequent Thrombolysis in Cerebral Infarction 3 result within 2 hours after computed tomography perfusion, were included. Computed tomography perfusion core volumes were assessed with both software applications with different thresholds for relative cerebral blood flow (rCBF). The results were compared with the FIV on computed tomography within 24 to 36 hours after recanalization. Bland-Altman was applied to display the levels of agreement and to evaluate systematic differences. RESULTS: Highest correlation between ischemic core volume and FIV without significant differences was found at a threshold of rCBF<38% for the RAPID software (r=0.89, P<0.001) and rCBF<25% for the Syngo software (r=0.87, P<0.001). Bland-Altman analysis revealed best agreement in these settings. In the vendor default settings (rCBF<30% for RAPID and rCBF<20% for Syngo) correlation between ischemic core volume and FIV was also high (RAPID: r=0.88, Syngo: r=0.86, P<0.001), but mean differences were significant (P<0.001). The risk of critical overestimation of the FIV was higher with rCBF<38% (RAPID) and rCBF<25% (Syngo) than in the default settings. CONCLUSIONS: By adjusting the rCBF thresholds, comparable results with reliable information on the FIV after complete recanalization can be obtained both with the RAPID and Syngo software. Keeping the software specific default settings means being more inclusive in patient selection, but forgo the highest possible accuracy in the estimation of the FIV.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/tratamiento farmacológico , Humanos , Perfusión , Imagen de Perfusión/métodos , Estudios Retrospectivos , Terapia Trombolítica , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE: Restless legs syndrome (RLS) is known to be associated with multiple sclerosis (MS) and may be caused by MS lesions in specific cerebral brain regions. Applying a voxel-wise lesion analysis, we tried to identify the contribution of cerebral MS lesions to RLS. METHODS: In this retrospective study, we established a cohort of people with MS with documented RLS and controls of people with MS without RLS matched disease severity. Diagnosis of MS and RLS was based on the current guidelines. The MS lesions were analyzed on T2-weighted magnetic resonance imaging scans (1.5 or 3 T). After manual delineation, lesion maps were converted into stereotaxic space. We generated a lesion overlap and performed a Liebermeister test with 4000 permutations to compare the absence or presence of RLS voxel-wise between patients with and without lesions in a given voxel. RESULTS: Forty of the patients with RLS and MS fulfilled the inclusion criteria. The voxel-wise analysis yielded associations between RLS and MS in the subcortex of the left gyrus precentralis. CONCLUSION: Our voxel-wise analysis shows associations in the subcortex of the left gyrus precentralis. Thus, our data suggests that a dysfunction of the efferent motor system due to cerebral lesions may contribute to the pathophysiology of RLS in MS.
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Esclerosis Múltiple , Síndrome de las Piernas Inquietas , Encéfalo/patología , Humanos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Síndrome de las Piernas Inquietas/complicaciones , Síndrome de las Piernas Inquietas/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Serotype 19A strains have emerged as a cause of invasive pneumococcal disease after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), and serotype 19A has now been included in the recent 13-valent vaccine (PCV13). Genetic analysis has revealed at least three different capsular serotype 19A subtypes, and nutritional environment-dependent variation of the 19A capsule structure has been reported. Pneumococcal vaccine effectiveness and serotyping accuracy might be impaired by structural differences in serotype 19A capsules. We therefore analyzed the distribution of 19A subtypes collected within a Swiss national surveillance program and determined capsule composition under different nutritional conditions with high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy. After the introduction of PCV7, a significant relative increase of subtype 19A-II and decrease of 19A-I occurred. Chemical analyses showed no difference in the composition as well as the linkage of 19A subtype capsular saccharides grown in defined and undefined growth media, which is consistent with a trisaccharide repeat unit composed of rhamnose, N-acetyl-mannosamine, and glucose. In summary, our study suggests that no structural variance dependent of the nutritional environment or the subtype exists. The serotype 19A subtype shift observed after the introduction of the PCV7 can therefore not be explained by selection of a capsule structure variant. However, capsule composition analysis of emerging 19A clones is recommended in cases where there is no other explanation for a selective advantage, such as antibiotic resistance or loss or acquisition of other virulence factors.
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Cápsulas Bacterianas/química , Infecciones Neumocócicas/microbiología , Polisacáridos/química , Streptococcus pneumoniae/fisiología , Cromatografía Liquida , Cromatografía de Gases y Espectrometría de Masas , Humanos , Espectroscopía de Resonancia Magnética , Vigilancia de la Población , Análisis de Regresión , Serogrupo , Serotipificación , Streptococcus pneumoniae/clasificaciónRESUMEN
Malignant gliomas can be counted to the most devastating tumors in humans. Novel therapies do not achieve significant prolonged survival rates. The cancer cells have an impact on the surrounding vital tissue and form tumor zones, which make up the tumor microenvironment. We investigated the effects of sunitinib, a small molecule multitargeted receptor tyrosine kinase inhibitor, on constituents of the tumor microenvironment such as gliomas, astrocytes, endothelial cells, and neurons. Sunitinib has a known anti-angiogenic effect. We found that sunitinib normalizes the aberrant tumor-derived vasculature and reduces tumor vessel pathologies (i.e. auto-loops). Sunitinib has only minor effects on the normal, physiological, non-proliferating vasculature. We found that neurons and astrocytes are protected by sunitinib against glutamate-induced cell death, whereas sunitinib acts as a toxin towards proliferating endothelial cells and tumor vessels. Moreover, sunitinib is effective in inducing glioma cell death. We determined the underlying pathways by which sunitinib operates as a toxin on gliomas and found vascular endothelial growth factor receptor 2 (VEGFR2, KDR/Flk1) as the main target to execute gliomatoxicity. The apoptosis-inducing effect of sunitinib can be mimicked by inhibition of VEGFR2. Knockdown of VEGFR2 can, in part, foster the resistance of glioma cells to receptor tyrosine kinase inhibitors. Furthermore, sunitinib alleviates tumor-induced neurodegeneration. Hence, we tested whether temozolomide treatment could be potentiated by sunitinib application. Here we show that sunitinib can amplify the effects of temozolomide in glioma cells. Thus, our data indicate that combined treatment with temozolomide does not abrogate the effects of sunitinib. In conclusion, we found that sunitinib acts as a gliomatoxic agent and at the same time carries out neuroprotective effects, reducing tumor-induced neurodegeneration. Thus, this report uncovered sunitinib's actions on the brain tumor microenvironment, revealing novel aspects for adjuvant approaches and new clinical assessment criteria when applied to brain tumor patients.
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Antineoplásicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Indoles/farmacología , Fármacos Neuroprotectores/farmacología , Pirroles/farmacología , Microambiente Tumoral/efectos de los fármacos , Inhibidores de la Angiogénesis/farmacología , Animales , Apoptosis/efectos de los fármacos , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Neoplasias Encefálicas/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Glioma/metabolismo , Humanos , Ratones , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Enfermedades Neurodegenerativas/tratamiento farmacológico , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratas , Roedores , Sunitinib , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Background and aims: General guideline recommendations in patients with intracerebral hemorrhage (ICH) include blood pressure-, temperature- and glucose management. The therapeutic effect of such a "care bundle" (blood pressure lowering, glycemic control, and treatment of pyrexia) on clinical outcomes becomes increasingly established. For the present study, we aimed to investigate associations of strict bundled care treatment (BCT) with clinical outcomes and characterize associations with key outcome effectors such as hematoma enlargement (HE) and peak perihemorrhagic edema (PHE). Methods: We screened consecutive ICH patients (n = 1,322) from the prospective UKER-ICH cohort study. BCT was defined as achieving and maintaining therapeutic ranges for systolic blood pressure (110-160 mmHg), glucose (80-180 mg/dL), and body temperature (35.5-37.5°C) over the first 72 h. The primary outcome was the functional outcome at 12 months (modified Rankin Scale (mRS) 0-3). Secondary outcomes included mortality at 12 months, the occurrence of hematoma enlargement, and the development of peak perihemorrhagic edema. Confounding was addressed by a doubly robust methodology to calculate the absolute treatment effect (ATE) and by calculating e-values. Results: A total of 681 patients remained for analysis, and 182 patients fulfilled all three BCT criteria and were compared to 499 controls. The ATE of BCT to achieve the primary outcome was 9.3%, 95% CI (1.7 to 16.9), p < 0.001; e-value: 3.1, CI (1.8). Mortality at 12 months was significantly reduced by BCT [ATE: -12.8%, 95% CI (-19.8 to -5.7), p < 0.001; e-value: 3.8, CI (2.2)], and no association was observed for HE or peak PHE. Significant drivers of BCT effect on the primary outcome were systolic blood pressure control (ATE: 15.9%) and maintenance of normothermia (ATE: 10.9%). Conclusion: Strict adherence to this "care bundle" over the first 72 h during acute hospital care in patients with ICH was independently associated with improved functional long-term outcome, driven by systolic blood pressure control and maintenance of normothermia. Our findings strongly warrant prospective validation to determine the generalizability especially in Western countries.Clinical trial registration:ClinicalTrials.gov, identifier [ID: NCT03183167].
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Acute ischemic stroke (AIS) is a leading global cause of mortality and morbidity. Improving long-term outcome predictions after thrombectomy can enhance treatment quality by supporting clinical decision-making. With the advent of interpretable deep learning methods in recent years, it is now possible to develop trustworthy, high-performing prediction models. This study introduces an uncertainty-aware, graph deep learning model that predicts endovascular thrombectomy outcomes using clinical features and imaging biomarkers. The model targets long-term functional outcomes, defined by the three-month modified Rankin Score (mRS), and mortality rates. A sample of 220 AIS patients in the anterior circulation who underwent endovascular thrombectomy (EVT) was included, with 81 (37%) demonstrating good outcomes (mRS ≤ 2). The performance of the different algorithms evaluated was comparable, with the maximum validation under the curve (AUC) reaching 0.87 using graph convolutional networks (GCN) for mRS prediction and 0.86 using fully connected networks (FCN) for mortality prediction. Moderate performance was obtained at admission (AUC of 0.76 using GCN), which improved to 0.84 post-thrombectomy and to 0.89 a day after stroke. Reliable uncertainty prediction of the model could be demonstrated.
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Aprendizaje Profundo , Accidente Cerebrovascular Isquémico , Humanos , Incertidumbre , Algoritmos , TrombectomíaRESUMEN
BACKGROUND: Abrupt visual impairment constitutes a medical urgency, necessitating an interdisciplinary diagnostic and therapeutic approach owing to the broad spectrum of potential etiologies, thereby engaging numerous medical specialties. CASE PRESENTATION: A 21-year-old Mixed White and Asian female patient, with medical history of nonsteroidal antiinflammatory drug-exacerbated respiratory disease necessitating previous sinus surgery, reported sudden monocular vision loss. Unremarkable ophthalmological examination of the fellow eye and hematological parameters, save for a slight elevation in lymphocytes and eosinophils, were observed. Imaging studies indicated recurrence of bilateral chronic rhinosinusitis with nasal polyps and a mucocele in the left sphenoid sinus, accompanied by bony structural deficits. Emergency revision sinus surgery, guided by navigation, was promptly performed. The patient received treatment with methylprednisolone, ceftriaxone, cyanocobalamin, pyridoxine, thiamine, and acetylsalicylic acid. During the hospital stay, she developed steroid-induced glaucoma, which was subsequently managed successfully. Negative microbiological swabs, along with pathohistological evidence of increased tissue eosinophilia and the patient's clinical history, led to the diagnosis of toxic retrobulbar neuritis secondary to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-associated chronic rhinosinusitis of the left sphenoid sinus. CONCLUSIONS: In cases of acute unilateral vision loss, optic neuritis is a highly probable differential diagnosis and may be induced by pathologies of the paranasal sinuses. Nonsteroidal antiinflammatory drug-exacerbated respiratory disease, a subtype of chronic rhinosinusitis, is associated with type 2 inflammation, which is increasingly recognized for its role in the pathogenesis of bronchial asthma, eosinophilic esophagitis, and atopic eczema. Clinicians should consider chronic rhinosinusitis as a potential differential diagnosis in unilateral visual loss and be cognizant of the rising significance of type 2 inflammations, which are relevant to a variety of diseases.
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Glaucoma , Neuritis Óptica , Sinusitis , Humanos , Femenino , Adulto Joven , Adulto , Seno Esfenoidal/diagnóstico por imagen , Sinusitis/tratamiento farmacológico , Neuritis Óptica/inducido químicamente , Neuritis Óptica/tratamiento farmacológico , Trastornos de la Visión , Ceguera/complicaciones , Enfermedad CrónicaRESUMEN
BACKGROUND: Hyperdense lesions in CT after EVT of LVO are common. These lesions are predictors for haemorrhages and an equivalent of the final infarct. The aim of this study based on FDCT was the evaluation of predisposing factors for these lesions. METHODS: Using a local database, 474 patients with mTICI ≥ 2B after EVT were recruited retrospectively. A postinterventional FDCT after recanalisation was analysed regarding such hyperdense lesions. This was correlated with a variety of items (demographics, past medical history, stroke assessment/treatment and short-/long-term follow-up). RESULTS: Significant differences were present in NHISS at admission, regarding time window, ASPECTS in initial NECT, location of the LVO, CT-perfusion (penumbra, mismatch ratio), haemostatic parameters (INR, aPTT), duration of EVT, number of EVT attempts, TICI, affected brain region, volume of demarcation and FDCT-ASPECTS. The ICH-rate, the volume of demarcation in follow-up NECT and the mRS at 90 days differed in association with these hyperdensities. INR, the location of demarcation, the volume of demarcation and the FDCT-ASPECTS could be demonstrated as independent factors for the development of such lesions. CONCLUSION: Our results support the prognostic value of hyperdense lesions after EVT. We identified the volume of the lesion, the affection of grey matter and the plasmatic coagulation system as independent factors for the development of such lesions.
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Objective: Hematoma expansion (HE) is the most important therapeutic target during acute care of patients with intracerebral hemorrhage (ICH). Imaging biomarkers such as non-contrast CT (NCCT) markers have been associated with increasing risk for HE. The aim of the present study was to evaluate the influence of NCCT markers with functional long-term outcome and with HE in patients with deep (basal ganglia and thalamus) ICH who represent an important subgroup of patients at the highest risk for functional deterioration with HE due to the eloquence of the affected brain region. Methods: From our prospective institutional database, all patients maximally treated with deep ICH were included and retrospectively analyzed. NCCT markers were recorded at diagnostic imaging, ICH volume characteristics were volumetrically evaluated, and all patients received follow-up imaging within 0-48 h. We explored associations of NCCT makers with unfavorable functional outcome, defined as modified Rankin scale 4-6, after 12 months and with HE. Bias and confounding were addressed by multivariable regression modeling. Results: In 322 patients with deep ICH, NCCT markers were distributed as follows: irregular shape: 69.6%, heterogenous density: 55.9%, hypodensities: 52.5%, island sign: 19.3%, black hole sign: 11.5%, and blend sign: 4.7%. Upon multivariable regression analyses, independent associations were documented with the functional outcome for irregular shape (aOR: 2.73, 95%CI: 1.42-5.22, p = 0.002), heterogenous density (aOR: 2.62, 95%CI: 1.40-4.90, p = 0.003) and island sign (aOR: 2.54, 95%CI: 1.05-6.14, p = 0.038), and with HE for heterogenous density (aOR: 5.01, 95%CI: 1.93-13.05, p = 0.001) and hypodensities (aOR: 3.75, 95%CI: 1.63-8.62, p = 0.002). Conclusion: NCCT markers are frequent in deep ICH patients and provide important clinical implications. Specifically, markers defined by diverging intra-hematomal densities provided associations with a 5-times higher risk for HE and a 2.5-times higher likelihood for unfavorable functional long-term outcome. Hence, these markers allow the identification of patients with deep ICH at high risk for clinical deterioration due to HE.
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We report the development of a powerful data management tool for chemical and biological data: CyBy(2). CyBy(2) is a structure-based information management tool used to store and visualize structural data alongside additional information such as project assignment, physical information, spectroscopic data, biological activity, functional data and synthetic procedures. The application consists of a database, an application server, used to query and update the database, and a client application with a rich graphical user interface (GUI) used to interact with the server.
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Sistemas de Administración de Bases de Datos , Diseño de Software , Interfaz Usuario-Computador , Biología/métodos , Química/métodosRESUMEN
PURPOSE: Treating cerebral dural arteriovenous fistulas (dAVFs) by transarterial embolization is an established endovascular approach but no data exist regarding the utility of using the newly introduced microcatheters with extra-long detachable tip. Aim of our study was to evaluate the value of these microcatheters and, additionally, of combining them with the simplified pressure cooker technique. METHODS: Twenty-nine patients treated for dAVF with transarterial embolization were enrolled. In a subgroup of fifteen patients the simplified pressure cooker technique was additionally applied. Demographics and characteristics were collected for patients and dAVFs and procedural details reviewed. The association between covariates and binary-coded occlusion status was evaluated. RESULTS: Microcatheter navigation into the target pedicle as well as application of the simplified pressure cooker technique were successful in all cases. Complete dAVF occlusion was reached in 69.0% at a single stage. In case of complete dAVF occlusion, embolization via only one pedicle was enough. Subgroup analysis revealed a higher occlusion status (80%) if using the simplified pressure cooker technique than if not (57%) but reached not significance level. CONCLUSION: Using microcatheters with extra-long detachable tip for dAVF embolization seems to offer a safe and effective treatment option with exceptional high occlusion rate at a single stage. The high navigability facilitates catheterization of a single selected target pedicle that is often enough to reach complete dAVF occlusion. Combining these microcatheters with the simplified pressure cooker technique turned out to be safe and easy to handle and might allow an increasing dAVF occlusion rate.
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OBJECTIVE: A prospective preoperative evaluation of 7 T ultra-high-field magnetic resonance imaging (MRI) in patients with suspected pituitary microadenomas for both adenoma detection and intrasellar localization compared with 3 T MRI was carried out. MATERIALS AND METHODS: Patients underwent prospective preoperative standardized 3 and 7 T MRI. A distinct qualitative (lesion detection, intrasellar lesion location) and quantitative (lesion diameters, T1/T2 signal intensity ratio of the lesion to normal pituitary gland tissue) analysis was performed, along with an evaluation of image quality (IQ) regarding overall IQ, anatomical parameters, and artifacts; the findings of the qualitative analysis were compared with intraoperative findings and endocrinological outcomes. RESULTS: Sixteen patients (mean age, 43 ± 16 years; 13 women) with pituitary microadenomas were included. Using 7 T MRI allowed the detection of 15 microadenomas-3 more than 3 T MRI. In addition, 7 T MRI allowed more precise lesion localization with 93.75% (15/16) agreement with intraoperative findings, compared with 75% (12/16) agreement using 3 T MRI. Lesion diameters showed no significant difference between 3 and 7 T MRI. T1 and T2 signal intensity ratio between microadenomas and normal pituitary gland tissue were higher in 7 T MRI than in 3 T MRI. The overall IQ and the IQ of each anatomical parameter of 7 T MRI were rated higher than those of 3 T MRI. No significant differences in susceptibility or head motion artifacts were observed between 3 and 7 T MRI; however, 7 T MRI was more susceptible to pulsation artifacts. CONCLUSION: Ultra-high-field MRI surpasses 3 T MRI in pituitary microadenoma detection and enables more precise delineation with higher correlation with intraoperative findings. Thus, 7 T sellar imaging is a promising option-especially in previously magnetic resonance-negative patients with endocrinologically confirmed hormone oversecretion-and helps reduce the need for invasive diagnostics.
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Adenoma , Neoplasias Hipofisarias , Adenoma/diagnóstico por imagen , Adenoma/cirugía , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Hipófisis/patología , Hipófisis/cirugía , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/patología , Estudios ProspectivosRESUMEN
Background: Innovative automated perfusion software solutions offer support in the management of acute stroke by providing information about the infarct core and penumbra. While the performance of different software solutions has mainly been investigated in patients with successful recanalization, the prognostic accuracy of the hypoperfusion maps in cases of futile recanalization has hardly been validated. Methods: In 39 patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation and poor revascularization (thrombolysis in cerebral infarction (TICI) 0-2a) after mechanical thrombectomy (MT), hypoperfusion analysis was performed using three different automated perfusion software solutions (A: RAPID, B: Brainomix e-CTP, C: Syngo.via). The hypoperfusion volumes (HV) as Tmax > 6 s were compared with the final infarct volumes (FIV) on follow-up CT 36−48 h after futile recanalization. Bland−Altman analysis was applied to display the levels of agreement and to evaluate systematic differences. Based on the median hypoperfusion intensity ratio (HIR, volumetric ratio of tissue with a Tmax > 10 s and Tmax > 6 s) patients were dichotomized into high- and low-HIR groups. Subgroup analysis with favorable (<0.6) and unfavorable (≥0.6) HIR was performed with respect to the FIV. HIR was correlated to clinical baseline and outcome parameters using Pearson's correlation. Results: Overall, there was good correlation without significant differences between the HVs and the FIVs with package A (r = 0.78, p < 0.001) being slightly superior to B and C. However, levels of agreement were very wide for all software applications in Bland-Altman analysis. In cases of large infarcts exceeding 150 mL the performance of the automated software solutions generally decreased. Subgroup analysis revealed the FIV to be generally underestimated in patients with HIR ≥ 0.6 (p < 0.05). In the subgroup with favorable HIR, however, there was a trend towards an overestimation of the FIV. Nevertheless, packages A and B showed good correlation between the HVs and FIVs without significant differences (p > 0.2), while only package C significantly overestimated the FIV (−54.6 ± 56.0 mL, p = 0.001). The rate of modified Rankin Scale (mRS) 0−3 after 3 months was significantly higher in favorable vs. unfavorable HIR (42.1% vs. 13.3%, p = 0.02). Lower HIR was associated with higher Alberta Stroke Program Early CT Score (ASPECTS) at presentation and on follow-up imaging, lower risk of malignant edema, and better outcome (p < 0.05). Conclusion: Overall, the performance of the automated perfusion software solutions to predict the FIV after futile recanalization is good, with decreasing accuracy in large infarcts exceeding 150 mL. However, depending on the HIR, FIV can be significantly over- and underestimated, with Syngo showing the widest range. Our results indicate that the HIR can serve as valuable parameter for outcome predictions and facilitate the decision whether or not to perform MT in delicate cases.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Infarto Cerebral/patología , Perfusión , Imagen de Perfusión/métodos , Pronóstico , Programas Informáticos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía/métodosRESUMEN
Importance: It is uncertain whether thrombectomy is associated with benefits in patients with prestroke disability. Objective: To evaluate the use of thrombectomy for patients with large vessel occlusion and prestroke disability. Design, Setting, and Participants: This cohort study included patients with large vessel occlusion stroke and prestroke disability (modified Rankin Scale score, 3 or 4) admitted to a single tertiary care center between January 1, 2006, and June 30, 2019 (controls: 2006-2015; thrombectomy: 2015-2019). Follow-up was conducted at 90 days. Data analysis was performed from November 1 to December 31, 2021. Exposures: Use of thrombectomy vs no thrombectomy. Main Outcomes and Measures: The primary outcome was functional recovery at 90 days defined as clinical recovery to the functional status before stroke onset. Secondary outcomes included functional dependency, mortality, early neurologic improvement, and recanalization. Results: Among 205 patients (149 women [72.7%]; median age, 82 years [IQR, 75-87 years]), 102 individuals (49.8%) received thrombectomy and 103 (50.2%) were controls. Thrombectomy was significantly associated with functional recovery (thrombectomy, 20 [19.6%]; controls, 8 [7.8%]; adjusted difference, 9.4%; 95% CI, 2.2% to 16.7%; P = .005). Secondary outcomes showed differences in mortality, early neurologic improvement, and recanalization in favor of thrombectomy treatment. The rate of functional dependency did not differ significantly between the 2 groups (adjusted difference, 8.9%; 95% CI, -2.5% to 20.2%; P = .13). The rate of functional recovery after thrombectomy was 44.0% for patients with early neurologic improvement, 29.4% for patients with small infarct volume (<50 mL), and 7.0% for patients with neither of these parameters. Conclusions and Relevance: Findings of this study suggest that selected patients with prestroke disability may benefit from thrombectomy. However, the thrombectomy-associated increase in functional recovery was small. Therefore, routine use of thrombectomy may not be beneficial among patients with a large ischemic core and infarct volumes less than 50 mL may be necessary to obtain functional recovery. Patients with higher chances of functional recovery are also at an increased risk of survival with substantial disability, indicating potential harms from the intervention; further studies are needed.
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Isquemia Encefálica , Accidente Cerebrovascular , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Infarto , Accidente Cerebrovascular/tratamiento farmacológico , TrombectomíaRESUMEN
Hippocampal-sparing radiotherapy (HSR) is a promising approach to alleviate cognitive side effects following cranial radiotherapy. Microstructural brain changes after irradiation have been demonstrated using Diffusion Tensor Imaging (DTI). However, evidence is conflicting for certain parameters and anatomic structures. This study examines the effects of radiation on white matter and hippocampal microstructure using DTI and evaluates whether these may be mitigated using HSR. A total of 35 tumor patients undergoing a prospective randomized controlled trial receiving either conventional or HSR underwent DTI before as well as 6, 12, 18, 24, and 30 (±3) months after radiotherapy. Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD), and Radial Diffusivity (RD) were measured in the hippocampus (CA), temporal, and frontal lobe white matter (TL, FL), and corpus callosum (CC). Longitudinal analysis was performed using linear mixed models. Analysis of the entire patient collective demonstrated an overall FACC decrease and RDCC increase compared to baseline in all follow-ups; ADCC decreased after 6 months, and MDCC increased after 12 months (p ≤ 0.001, 0.001, 0.007, 0.018). ADTL decreased after 24 and 30 months (p ≤ 0.004, 0.009). Hippocampal FA increased after 6 and 12 months, driven by a distinct increase in ADCA and MDCA, with RDCA not increasing until 30 months after radiotherapy (p ≤ 0.011, 0.039, 0.005, 0.040, 0.019). Mean radiation dose correlated positively with hippocampal FA (p < 0.001). These findings may indicate complex pathophysiological changes in cerebral microstructures after radiation, insufficiently explained by conventional DTI models. Hippocampal microstructure differed between patients undergoing HSR and conventional cranial radiotherapy after 6 months with a higher ADCA in the HSR subgroup (p ≤ 0.034).
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The Fmoc protection group is among the most commonly used protection groups for the amino function. A fast method for the thermal deavage of this protection group under base-free conditions without the need for dibenzofulvene scavengers is presented. The advantages of this method include straightforward testability by means of a simple high-temperature NMR experiment, usually high yields, and good selectivity towards the BOC protection group and t-butyl ethers.
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Aminoácidos/química , Fluorenos/química , Péptidos/síntesis química , Espectroscopía de Resonancia MagnéticaRESUMEN
We present the development of CyBy2, a versatile framework for chemical data management written in purely functional style in Scala, a modern multi-paradigm programming language. Together with the core libraries we provide a fully functional example implementation of a HTTP server together with a single page web client with powerful querying and visualization capabilities, providing essential functionality for people working in the field of organic and medicinal chemistry. The main focus of CyBy2 are the diverse needs of different research groups in the field and therefore the flexibility required from the underlying data model. Techniques for writing type level specifications giving strong guarantees about the correctness of the implementation are described, together with the resulting gain in confidence during refactoring. Finally we talk about the advantages of using a single code base from which the server, the client and the software's documentation pages are being generated. We conclude with a comparison with existing open source solutions. All code described in this article is published under version 3 of the GNU General Public License and available from GitHub including an example implementation of both backend and frontend together with documentation how to download and compile the software (available at https://github.com/stefan-hoeck/cyby2).
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Labeling decisions for core labeling and/or local labeling capture the outcome of all discussions on the product statements that are necessary to ensure safe and effective handling of pharmaceutical products, with a special focus on the decision concerning known, suspected, or hypothetical risks. Such decisions may determine if a topic is to be included in the label or provide a rationale for exclusion from the label. The need to provide special advice to users and the type of advice (eg, contraindications, precautions) are subject to labeling decisions as well. While the problem is well known to pharmaceutical companies, and technical solutions such as XML-based authoring/coding systems try to offer support from the information technology sector to handle the business problem, the current identification of medicinal products (IDMP) requirements raised by health authorities worldwide have put a new focus on the problem. This article will elaborate on the basic business problem and its requirements with respect to a solution.