RESUMEN

BACKGROUND: Baseline anemia is associated with poor intracerebral hemorrhage (ICH) outcomes. However, underlying drivers for anemia and whether anemia development after ICH impacts clinical outcomes are unknown. We hypothesized that inflammation drives anemia development after ICH and assessed their relationship to outcomes. METHODS AND RESULTS: Patients with serial hemoglobin and iron biomarker concentrations from the HIDEF (High-Dose Deferoxamine in Intracerebral Hemorrhage) trial were analyzed. Adjusted linear mixed models assessed laboratory changes over time. Of 42 patients, significant decrements in hemoglobin occurred with anemia increasing from 19% to 45% by day 5. Anemia of inflammation iron biomarker criteria was met in 88%. A separate cohort of 521 patients with ICH with more granular serial hemoglobin and long-term neurological outcome data was also investigated. Separate regression models assessed whether (1) systemic inflammatory response syndrome (SIRS) scores related to hemoglobin changes over time and (2) hemoglobin changes related to poor 90-day outcome. In this cohort, anemia prevalence increased from 30% to 71% within 2 days of admission yet persisted beyond this time. Elevated systemic inflammatory response syndrome was associated with greater hemoglobin decrements over time (adjusted parameter estimate: -0.27 [95% CI, -0.37 to -0.17]) and greater hemoglobin decrements were associated with poor outcomes (adjusted odds ratio per 1 g/dL increase, 0.76 [95% CI, 0.62-0.93]) independent to inflammation and ICH severity. CONCLUSIONS: We identified novel findings that acute anemia development after ICH is common, rapid, and related to inflammation. Because anemia development is associated with poor outcomes, further work is required to clarify if anemia, or its underlying drivers, are modifiable treatment targets that can improve ICH outcomes. REGISTRATION: https://www.clinicaltrials.gov Unique identifier: NCT01662895.

Asunto(s)

Anemia , Biomarcadores , Hemorragia Cerebral , Hemoglobinas , Inflamación , Humanos , Hemorragia Cerebral/sangre , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiología , Masculino , Femenino , Anemia/sangre , Anemia/diagnóstico , Anemia/epidemiología , Anciano , Persona de Mediana Edad , Biomarcadores/sangre , Hemoglobinas/metabolismo , Hemoglobinas/análisis , Inflamación/sangre , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Deferoxamina/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Hierro/sangre , Prevalencia

RESUMEN

Background: Laboratory monitoring is not recommended when subcutaneous unfractionated heparin (SQ-UFH) is administered at prophylactic doses. However, aPTT prolongation and associated hemorrhage has been reported in the neurocritically ill. At our institution, Neuroscience Intensive Care Unit (Neuro-ICU) patients with prolonged aPTT are further evaluated with a follow up aPTT and anti-factor Xa. Purpose: The purpose of this study was to describe concordance between aPTT and anti-factor Xa in neurocritically ill patients receiving prophylactic SQ-UFH with evidence of aPTT prolongation. Methods: A retrospective chart review of adult patients admitted to the Neuro-ICU from June 2017 to June 2019 was performed. Patients were included if they received SQ-UFH with aPTT levels and at least one anti-factor Xa level drawn within one hour of each other. Concordance between paired aPTT and anti-factor Xa was evaluated using Cohen's weighted kappa. Results: Forty two patients with 56 paired aPTT and anti-factor Xa levels were included. The most prescribed SQ-UFH regimen was 5000 units every 8 hours (60.7%) and anti-factor Xa levels were drawn a median (IQR) of 5.7 (3.1-10.7) hours after the SQ-UFH dose. Only 16 (28.6%) pairs were in concordance. The analysis showed a weighted kappa of .09; 95% CI [-.05 to .22] indicating poor agreement. Conclusions: In neurocritically ill patients receiving prophylactic SQ-UFH with aPTT prolongation, there was poor concordance between aPTT and anti-factor Xa. This suggests that aPTT prolongation may not be solely driven by heparin activity and further evaluation of mechanistic drivers for coagulopathy in this population is necessary.

RESUMEN

OBJECTIVES: Delirium is an acute brain dysfunction that has been correlated with adverse mental health outcomes, such as depression and posttraumatic stress disorder (PTSD). However, delirium has not been studied in relation to mental health outcomes after cerebrovascular events. This study aimed to examine the incidence of PTSD after nontraumatic intracerebral hemorrhage (ICH) and identify new predictors of poststroke PTSD symptoms. METHODS: Clinical data were collected from 205 patients diagnosed with nontraumatic ICH. Demographics and hospital course data were examined. Univariate and multivariable correlational analyses were performed to determine predictors of PTSD symptoms. PTSD symptoms were assessed using PTSD checklist-civilian version (PCL-C) scores. RESULTS: Diagnostic criteria for a positive PTSD screen (PCL-C score ≥44) were met by 13.7%, 20.2%, and 11.6% of nontraumatic patients with ICH at 3, 6, and 12 months, respectively. On univariate analysis, younger age, female sex, unemployed, and in-hospital delirium were correlated with higher PCL-C scores. In multivariable models, younger age, female sex, unemployed, in-hospital delirium, and a previous anxiety or depression diagnosis were associated with higher PCL-C scores at different follow-up times. Modified Rankin Scale scores were also positively correlated with PCL-C scores at each time point. CONCLUSIONS: Delirium, previous psychiatric history, younger age, female sex, and unemployment status were found to be associated with a greater degree of posthemorrhagic stroke PTSD symptoms. More significant PTSD symptoms were also correlated with greater functional impairment. A better understanding of patient susceptibility to PTSD symptoms may help providers coordinate earlier interventions.

Asunto(s)

Delirio , Trastornos por Estrés Postraumático , Accidente Cerebrovascular , Humanos , Femenino , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/etiología , Trastornos por Estrés Postraumático/diagnóstico , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiología , Delirio/diagnóstico , Delirio/epidemiología , Delirio/etiología

RESUMEN

BACKGROUND: While clinical guidelines provide a framework for hospital management of spontaneous intracerebral hemorrhage (ICH), variation in the resource use and costs of these services exists. We sought to perform a systematic literature review to assess the evidence on hospital resource use and costs associated with management of adult patients with ICH, as well as identify factors that impact variation in such hospital resource use and costs, regarding clinical characteristics and delivery of services. METHODS: A systematic literature review was performed using PubMed, Cochrane Central Register of Controlled Trials, and Ovid MEDLINE(R) 1946 to present. Articles were assessed against inclusion and exclusion criteria. Study design, ICH sample size, population, setting, objective, hospital characteristics, hospital resource use and cost data, and main study findings were abstracted. RESULTS: In total, 43 studies met the inclusion criteria. Pertinent clinical characteristics that increased hospital resource use included presence of comorbidities and baseline ICH severity. Aspects of service delivery that greatly impacted hospital resource consumption included intensive care unit length of stay and performance of surgical procedures and intensive care procedures. CONCLUSIONS: Hospital resource use and costs for patients with ICH were high and differed widely across studies. Making concrete conclusions on hospital resources and costs for ICH care was constrained, given methodologic and patient variation in the studies. Future research should evaluate the long-term cost-effectiveness of ICH treatment interventions and use specific economic evaluation guidelines and common data elements to mitigate study variation.

Asunto(s)

Hemorragia Cerebral , Unidades de Cuidados Intensivos , Adulto , Hemorragia Cerebral/terapia , Análisis Costo-Beneficio , Hospitales , Humanos

RESUMEN

In forensic investigations involving stolen and crashed vehicles, examining airbags for the presence of saliva is useful strategy in order to try and establish who the driver of the vehicle may have been. The use of an evaluative approach in these types of investigations allows the forensic scientist to evaluate the significance of the evidence with regard to two alternative hypothesis. The presence of saliva on an airbag may be the result of the driver coming into contact with it during an impact. Alternatively, the saliva may have transferred to the airbag from another area in the vehicle following its deployment. To address this question and attach significance to this finding, a dataset on the prevalence and persistence of saliva is required, alongside relevant background information on the case. The purpose of this study was to determine if saliva matching the main driver of a vehicle is present in the areas immediately surrounding the driver's section, and also to determine the persistence of saliva in vehicles. Salivary-α-amylase was detected in 53% of all samples collected from vehicles. Saliva positive samples yielded statistically significantly (p<0.05) more DNA than saliva negative samples. There was no statistical difference in DNA yields from the different areas sampled in the vehicles. The steering wheel was observed to have the greatest number of saliva positive samples (80%). The driver's DNA profile was detected in 72% of the total samples taken. We demonstrated that saliva can persist for at least ten days in vehicles in daily use. This study has produced a useful dataset that can be utilised under certain conditions by forensic investigators when taking an evaluative approach to these particular types of forensic investigations.

Asunto(s)

Automóviles , ADN/análisis , Saliva/química , Dermatoglifia del ADN , Humanos , Reacción en Cadena de la Polimerasa , Prevalencia , alfa-Amilasas Salivales/análisis , Manejo de Especímenes

RESUMEN

PURPOSE: To identify novel technologies pertinent to the prevention, diagnosis, treatment, and rehabilitation of ischemic stroke, and recommend the technologies that show the most promise in advancing ischemic stroke care. METHOD: A systematic literature search on PubMed and Medscape was performed. Articles were assessed based on pre-determined criteria. Included journal articles were evaluated for specific characteristics and reviewed according to a structured paradigm. A search on www.clinicaltrials.gov was performed to identify pre-clinical ischemic stroke technological interventions. All clinical trial results were included. An additional search on PubMed was conducted to identify studies on robotic neuroendovascular procedures. RESULTS: Thirty journal articles and five clinical trials were analyzed. Articles were categorized as follows: six studies pertinent to pre-morbidity and prevention of ischemic stroke, three studies relevant to the diagnosis of ischemic stroke, 16 studies about post-ischemic stroke rehabilitation, and five studies on robotic neuroendovascular interventions. CONCLUSIONS: Novel technologies across the spectrum of ischemic stroke care were identified, and the ones that appear to have the most clinical utility are recommended. Future investigation of the feasibility and long-term efficacy of the recommended technologies in clinical settings is warranted.

Asunto(s)

Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Robótica , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Isquemia Encefálica/complicaciones , Isquemia Encefálica/terapia , Humanos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia

RESUMEN

BACKGROUND AND PURPOSE: Preclinical and clinical studies have suggested a potential benefit from COX-2 inhibition on secondary injury activation after spontaneous intracerebral hemorrhage (ICH). The aim of this study was to investigate the effect of pre-admission NSAID use on functional recovery in spontaneous ICH patients. METHODS: Consecutive adult ICH patients enrolled in the Intracerebral Hemorrhage Outcomes Project (2009-2018) with available 90-day follow-up data were included. Patients were categorized as NSAID (daily COX inhibitor use ≤ 7 days prior to ICH) and non-NSAID users (no daily COX inhibitor use ≤ 7 days prior to ICH). Primary outcome was the ordinal 90-day modified Rankin Scale (mRS) score. Outcomes were compared between cohorts using multivariable regression and propensity score-matched analyses. A secondary analysis excluding aspirin users was performed. RESULTS: The NSAID and non-NSAID cohorts comprised 228 and 361 patients, respectively. After 1:1 matching, the matched cohorts each comprised 140 patients. The 90-day mRS were comparable between the NSAID and non-NSAID cohorts in both the unmatched (aOR = 0.914 [0.626-1.336], p = 0.644) and matched (aOR = 0.650 [0.392-1.080], p = 0.097) analyses. The likelihood of recurrent ICH at 90 days was also comparable between the NSAID and non-NSAID cohorts in both the unmatched (aOR = 0.845 [0.359-1.992], p = 0.701) and matched analyses (aOR = 0.732 [0.241-2.220], p = 0.581). In the secondary analysis, the non-aspirin NSAID and non-NSAID cohorts comprised 38 and 361 patients, respectively. After 1:1 matching, the matched cohorts each comprised 38 patients. The 90-day mRS were comparable between the non-aspirin NSAID and non-NSAID cohorts in both the unmatched (aOR = 0.615 [0.343-1.101], p = 0.102) and matched (aOR = 0.525 [0.219-1.254], p = 0.147) analyses. The likelihood of recurrent ICH at 90 days was also comparable between the non-aspirin NSAID and non-NSAID cohorts in both the unmatched (aOR = 2.644 [0.258-27.091], p = 0.413) and matched (aOR = 2.586 [0.228-29.309], p = 0.443) analyses. After the exclusion of patients with DNR or withdrawal of care status, NSAID use was associated with lower mRS at 90 days (aOR = 0.379 [0.212-0.679], p = 0.001), lower mRS at hospital discharge (aOR = 0.505 [0.278-0.919], p = 0.025) and lower 90-day mortality rates (aOR = 0.309 [0.108-0.877], p = 0.027). CONCLUSIONS: History of nonselective COX inhibition may affect functional outcomes in ICH patients. Pre-admission NSAID use did not appear to worsen the severity of presenting ICH or increase the risk of recurrent ICH. Additional clinical studies may be warranted to investigate the effects of pre-admission NSAID use on ICH outcomes.

Asunto(s)

Hemorragia Cerebral , Preparaciones Farmacéuticas , Adulto , Antiinflamatorios , Antiinflamatorios no Esteroideos/efectos adversos , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/tratamiento farmacológico , Humanos , Recuperación de la Función

RESUMEN

BACKGROUND: Smooth muscle cells (SMCs) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration, and transdifferentiation into other cell types. Yet how SMCs contribute to the pathophysiology of atherosclerosis remains elusive. METHODS: To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques. We also performed cell biology experiments on isolated SMC-derived cells, conducted integrative human genomics, and used pharmacological studies targeting SMC-derived cells both in vivo and in vitro. RESULTS: We found that SMCs transitioned to an intermediate cell state during atherosclerosis, which was also found in human atherosclerotic plaques of carotid and coronary arteries. SMC-derived intermediate cells, termed "SEM" cells (stem cell, endothelial cell, monocyte), were multipotent and could differentiate into macrophage-like and fibrochondrocyte-like cells, as well as return toward the SMC phenotype. Retinoic acid (RA) signaling was identified as a regulator of SMC to SEM cell transition, and RA signaling was dysregulated in symptomatic human atherosclerosis. Human genomics revealed enrichment of genome-wide association study signals for coronary artery disease in RA signaling target gene loci and correlation between coronary artery disease risk alleles and repressed expression of these genes. Activation of RA signaling by all-trans RA, an anticancer drug for acute promyelocytic leukemia, blocked SMC transition to SEM cells, reduced atherosclerotic burden, and promoted fibrous cap stability. CONCLUSIONS: Integration of cell-specific fate mapping, single-cell genomics, and human genetics adds novel insights into the complexity of SMC biology and reveals regulatory pathways for therapeutic targeting of SMC transitions in atherosclerotic cardiovascular disease.

Asunto(s)

Aterosclerosis/genética , Aterosclerosis/patología , Diferenciación Celular/fisiología , Genómica/métodos , Miocitos del Músculo Liso/patología , Fenotipo , Animales , Aterosclerosis/terapia , Desdiferenciación Celular/fisiología , Movimiento Celular/fisiología , Transdiferenciación Celular/fisiología , Células Cultivadas , Femenino , Terapia Genética/tendencias , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Miocitos del Músculo Liso/fisiología , Análisis de Secuencia de ARN/métodos

Asunto(s)

Amantadina/uso terapéutico , Lesiones Traumáticas del Encéfalo/complicaciones , Encéfalo/fisiopatología , Trastornos de la Conciencia/fisiopatología , Dopaminérgicos/uso terapéutico , Recuperación de la Función/fisiología , Trastornos de la Conciencia/tratamiento farmacológico , Trastornos de la Conciencia/etiología , Electroencefalografía , Humanos

RESUMEN

Cellular material derived from contact traces can be transferred via many direct and indirect routes, with the manner of contact and the time of transfer (in relation to the alleged crime-event) having an impact on whether DNA is recovered from the surface and a reportable profile generated. In an effort to acquire information on the transfer and recovery of DNA traces from clothing items worn during scenarios commonly encountered in casework, upper garments were worn during a normal working day before individuals were paired to embrace one another ('contact'), go on an outing together ('close proximity'), or individually asked to spend a day in another person's environment ('physical absence'). Each prescribed activity was repeated by sixteen individuals across four countries, and was the last activity performed before the garment was removed. Samples were collected from several areas of the upper garments and processed from DNA extraction through to profiling within the laboratory of the country in which the individual resided. Activities relating to the garment prior to and during wearing, including the prescribed activity, were recorded by the participant and considered during the interpretation of results. In addition to obtaining reference profiles from the wearer and their activity partner, DNA profiles from the wearers' close associates identified in the questionnaire were obtained to assess the impact of background DNA transferred prior to the prescribed activity. The wearer was typically, but not always, observed as the major contributor to the profiles obtained. DNA from the activity partner was observed on several areas of the garment following the embrace and after temporarily occupying another person's space. Particular areas of the garment were more prone to acquiring the hugging partner or office owner's DNA than others, and whether they were observed as the major or minor component was activity dependent. For each of the pairs, no DNA from the activity partner was acquired by the garments during the outing, even though both participants were in close proximity. This study provides empirical data on the transfer, persistence, prevalence and recovery of DNA from clothing items, and enables a better understanding of the mechanisms which lead to the transfer and detectability of DNA traces in different scenarios.

Asunto(s)

Vestuario , Dermatoglifia del ADN , ADN/análisis , Tacto , Humanos , Laboratorios

RESUMEN

Background and Purpose- Perihematomal edema (PHE) is a promising surrogate marker of secondary brain injury in patients with spontaneous intracerebral hemorrhage, but it can be challenging to accurately and rapidly quantify. The aims of this study are to derive and internally validate a fully automated segmentation algorithm for volumetric analysis of PHE. Methods- Inpatient computed tomography scans of 400 consecutive adults with spontaneous, supratentorial intracerebral hemorrhage enrolled in the Intracerebral Hemorrhage Outcomes Project (2009-2018) were separated into training (n=360) and test (n=40) datasets. A fully automated segmentation algorithm was derived from manual segmentations in the training dataset using convolutional neural networks, and its performance was compared with that of manual and semiautomated segmentation methods in the test dataset. Results- The mean volumetric dice similarity coefficients for the fully automated segmentation algorithm were 0.838±0.294 and 0.843±0.293 with manual and semiautomated segmentation methods as reference standards, respectively. PHE volumes derived from the fully automated versus manual (r=0.959; P<0.0001), fully automated versus semiautomated (r=0.960; P<0.0001), and semiautomated versus manual (r=0.961; P<0.0001) segmentation methods had strong between-group correlations. The fully automated segmentation algorithm (mean 18.0±1.8 seconds/scan) quantified PHE volumes at a significantly faster rate than both of the manual (mean 316.4±168.8 seconds/scan; P<0.0001) and semiautomated (mean 480.5±295.3 seconds/scan; P<0.0001) segmentation methods. Conclusions- The fully automated segmentation algorithm accurately quantified PHE volumes from computed tomography scans of supratentorial intracerebral hemorrhage patients with high fidelity and greater efficiency compared with manual and semiautomated segmentation methods. External validation of fully automated segmentation for assessment of PHE is warranted.

Asunto(s)

Algoritmos , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/etiología , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Hematoma/complicaciones , Adulto , Automatización , Biomarcadores , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Neuroimagen , Tomografía Computarizada por Rayos X , Resultado del Tratamiento

RESUMEN

BACKGROUND AND OBJECTIVE: Functional outcome after spontaneous intracerebral hemorrhage (ICH) may vary depending on hematoma volume and location. We assessed the interaction between hematoma volume and location, and modified the original ICH score to include such an interaction. METHODS: Consecutive ICH patients were enrolled in the Intracerebral Hemorrhage Outcomes Project from 2009 to 2017. Inclusion criteria were age≥18 years, baseline modified Rankin Scale (mRS) score 0-2, neuroimaging, and follow-up. Functional dependence and mortality were defined as 90-day mRS>2 and death, respectively. A location ICH score was developed using multivariable regression and area under the receiver operator characteristic curve (AUROC) analyses. RESULTS: The study cohort comprised 311 patients, and the derivation and validation cohorts comprised 209 and 102 patients, respectively. Interactions between hematoma volume and location predicted functional dependence (p = 0.008) and mortality (p = 0.025). The location ICH score comprised age≥80 years (1 point), Glasgow Coma Scale score (3-9 = 2 points; 10-13 = 1 point), volume-location (lobar:≥24 mL=2 points, 21-24 mL=1 point; deep:≥8 mL=2 points, 7-8 mL=1 point; brainstem:≥6 mL=2 points, 3-6 mL=1 point; cerebellum:≥24 mL=2 points, 12-24 mL=1 point), and intraventricular hemorrhage (1 point). AUROC of the location ICH score was higher in functional dependence (0.883 vs. 0.770, p = 0.002) but not mortality (0.838 vs. 0.841, p = 0.918) discrimination compared to the original ICH score. CONCLUSIONS: The interaction between hematoma volume and location exerted an independent effect on outcomes. Excellent discrimination of functional dependence and mortality was observed with incorporation of location-specific volume thresholds into a prediction model. Therefore, the volume-location relationship plays an important role in ICH outcome prediction.

Asunto(s)

Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/patología , Hematoma/mortalidad , Hematoma/patología , Adulto , Femenino , Estado Funcional , Escala de Coma de Glasgow/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Neuroimagen , Pronóstico , Tomografía Computarizada por Rayos X , Adulto Joven

RESUMEN

Background and Purpose- Hematoma volume measurements influence prognosis and treatment decisions in patients with spontaneous intracerebral hemorrhage (ICH). The aims of this study are to derive and validate a fully automated segmentation algorithm for ICH volumetric analysis using deep learning methods. Methods- In-patient computed tomography scans of 300 consecutive adults (age ≥18 years) with spontaneous, supratentorial ICH who were enrolled in the ICHOP (Intracerebral Hemorrhage Outcomes Project; 2009-2018) were separated into training (n=260) and test (n=40) datasets. A fully automated segmentation algorithm was derived using convolutional neural networks, and it was trained on manual segmentations from the training dataset. The algorithm's performance was assessed against manual and semiautomated segmentation methods in the test dataset. Results- The mean volumetric Dice similarity coefficients for the fully automated segmentation algorithm when tested against manual and semiautomated segmentation methods were 0.894±0.264 and 0.905±0.254, respectively. ICH volumes derived from fully automated versus manual (R2=0.981; P<0.0001), fully automated versus semiautomated (R2=0.978; P<0.0001), and semiautomated versus manual (R2=0.990; P<0001) segmentation methods had strong between-group correlations. The fully automated segmentation algorithm (mean 12.0±2.7 s/scan) was significantly faster than both of the manual (mean 201.5±92.2 s/scan; P<0.001) and semiautomated (mean 288.58±160.3 s/scan; P<0.001) segmentation methods. Conclusions- The fully automated segmentation algorithm quantified hematoma volumes from computed tomography scans of supratentorial ICH patients with similar accuracy and substantially greater efficiency compared with manual and semiautomated segmentation methods. External validation of the fully automated segmentation algorithm is warranted.

Asunto(s)

Hemorragia Cerebral/diagnóstico por imagen , Aprendizaje Profundo , Hematoma/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Neuroimagen/métodos , Hemorragia Cerebral/patología , Hematoma/patología , Humanos

RESUMEN

OBJECTIVE: Delayed cerebral ischemia (DCI) is a significant contributor to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). The neurotoxin 3-aminopropanal (3-AP) is upregulated in cerebral ischemia. This phase II clinical trial evaluated the efficacy of tiopronin in reducing CSF 3-AP levels in patients with aSAH. METHODS: In this prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial, 60 patients were assigned to receive tiopronin or placebo in a 1:1 ratio. Treatment was commenced within 96 hours after aSAH onset, administered at a dose of 3 g daily, and continued until 14 days after aSAH or hospital discharge, whichever occurred earlier. The primary efficacy outcome was the CSF 3-AP level at 7 ± 1 days after aSAH. RESULTS: Of the 60 enrolled patients, 29 (97%) and 27 (93%) in the tiopronin and placebo arms, respectively, received more than one dose of the study drug or placebo. At post-aSAH day 7 ± 1, CSF samples were available in 41% (n = 12/29) and 48% (n = 13/27) of patients in the tiopronin and placebo arms, respectively. No difference in CSF 3-AP levels at post-aSAH day 7 ± 1 was observed between the study arms (11 ± 12 nmol/mL vs 13 ± 18 nmol/mL; p = 0.766). Prespecified adverse events led to early treatment cessation for 4 patients in the tiopronin arm and 2 in the placebo arm. CONCLUSIONS: The power of this study was affected by missing data. Therefore, the authors could not establish or refute an effect of tiopronin on CSF 3-AP levels. Additional observational studies investigating the role of 3-AP as a biomarker for DCI may be warranted prior to its use as a molecular target in future clinical trials.Clinical trial registration no.: NCT01095731 (ClinicalTrials.gov).

RESUMEN

BACKGROUND: Nicotine may have neuroprotective effects on the injured brain through modulation of the cholinergic anti-inflammatory pathway. AIMS: This study aimed to evaluate the relationship between cigarette smoking and outcomes in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: This was a retrospective review of consecutive ICH patients enrolled in the ICH Outcomes Project from 2009 to 2017. Patients with age ≥18 years and baseline modified Rankin Scale (mRS) score 0-2 were included. Smoking patterns were categorized as recent smoker (≤30 days prior to ICH) and not recent smoker (>30 days prior to ICH). Not recent smokers were further categorized into former smokers and nonsmokers. The primary outcome was good outcome (90-day mRS ≤ 2). Secondary outcomes were excellent outcome (90-day mRS 0-1), 90-day Barthel Index, and in-hospital and 90-day mortality. RESULTS: The study cohort comprised 545 patients, including 60 recent smokers and 485 not recent smokers. Recent smokers had higher rates of good (35% versus 23%; odds ratio [OR] = 1.787, P = .047) and excellent (25% versus 13%; OR = 2.220, P = .015) outcomes compared to not recent smokers. These differences were not significant after baseline adjustments. Recent smokers had higher rates of good (36% versus 24%; OR = 1.732, P = .063) and excellent (25% versus 13%; OR = 2.203, P = .018) outcomes compared to nonsmokers. These differences were not significant after baseline adjustments. A 90-day Barthel Index, in-hospital, and 90-day mortality were comparable between recent and not recent smokers, recent and nonsmokers, and former and nonsmokers. CONCLUSIONS: Despite potential neuroprotective effects of nicotine found in cigarettes, these may be outweighed by the detrimental effects of cigarette smoking on health outcomes.

Asunto(s)

Encéfalo/fisiopatología , Hemorragia Cerebral/fisiopatología , No Fumadores , Fumadores , Fumar/efectos adversos , Adulto , Anciano , Encéfalo/efectos de los fármacos , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/mortalidad , Bases de Datos Factuales , Evaluación de la Discapacidad , Femenino , Estado de Salud , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/efectos adversos , Nicotina/administración & dosificación , Nicotina/efectos adversos , Agonistas Nicotínicos/administración & dosificación , Agonistas Nicotínicos/efectos adversos , Valor Predictivo de las Pruebas , Pronóstico , Factores Protectores , Recuperación de la Función , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Fumar/mortalidad , Cese del Hábito de Fumar , Factores de Tiempo

RESUMEN

Among the various items recovered from crime scenes or persons involved in a crime event, clothing items are commonly encountered and submitted for forensic DNA sampling. Depending on the case circumstances and the activity-of-interest, sampling of the garment may concentrate on collecting DNA from the wearer, or from one or more offenders who have allegedly contacted the item and/or wearer. Relative to the targeted DNA, background DNA already residing on the item from previous contacts, or transferred during or after the crime event, may also be collected during sampling and observed in the resultant DNA profile. Given our limited understanding of how, and from where, background DNA is derived on clothing, research on the transfer, persistence, prevalence, and recovery (TPPR) of DNA traces from upper garments was conducted by four laboratories. Samples were collected from several areas of two garments, each worn on separate working or non-working days and individually owned by four individuals from each of the four laboratories, and processed from DNA extraction through to profiling. Questionnaires documented activities relating to the garment prior to and during wearing, and reference profiles were obtained from the wearer and their close associates identified in the questionnaire. Among the 448 profiles generated, variation in the DNA quantity, composition of the profiles, and inclusion/exclusion of the wearer and their close associates was observed among the collaborating laboratories, participants, garments worn on different occasions, and garment areas sampled.

Asunto(s)

Vestuario , Dermatoglifia del ADN , ADN/análisis , Humanos , Laboratorios , Reacción en Cadena de la Polimerasa , Prevalencia , Control de Calidad , Manejo de Especímenes

Asunto(s)

Edema Encefálico , Hemorragia Cerebral , Hematoma , Edema Encefálico/fisiopatología , Edema Encefálico/terapia , Hemorragia Cerebral/fisiopatología , Hemorragia Cerebral/terapia , Femenino , Hematoma/fisiopatología , Hematoma/terapia , Humanos , Masculino

Asunto(s)

Estenosis Carotídea , Endarterectomía Carotidea , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Accidente Cerebrovascular , Arterias Carótidas , Humanos

RESUMEN

BACKGROUND/PURPOSE: Blood type has become an increasingly recognized risk factor for coagulopathy. We explored the association between blood type and hematoma expansion (HE) after intracerebral hemorrhage (ICH). METHODS: Spontaneous ICH patients prospectively enrolled in an ongoing ICH cohort study at Columbia University Irving Medical Center from 2009 to 2016 were evaluated. Primary ICH patients with admission blood type testing were evaluated for HE differences, defined as > 33% relative HE. The association of blood type with radiographic HE outcomes was assessed using multivariable logistic regression models. The association of blood type and poor clinical outcomes using modified Rankin Scale (mRS 4-6) was additionally explored. RESULTS: Of 272 ICH patients with blood type data and neuroimaging available to determine HE, there were 146 (54%) type-O, 82 (30%) type-A, 34 (13%) type-B, and 10 (3%) type-AB patients. No significant baseline demographic, clinical, or radiographic differences were noted between blood types. Type-B blood was associated with more HE compared to other blood types (OR 2.82; 95% CI 1.23-6.45) after adjusting for known covariates of HE (anticoagulant use, time to admission computed tomography scan, and baseline hematoma volume). No associations with blood type and poor 3 month mRS were identified, but these analyses were limited secondary to our smaller cohort. CONCLUSIONS: There may be differences in HE after ICH in patients with different blood types. Further work is required to replicate these findings and identify the pathophysiologic mechanisms behind coagulopathy between blood types after ICH.

Asunto(s)

Sistema del Grupo Sanguíneo ABO , Hemorragia Cerebral/sangre , Hemorragia Cerebral/complicaciones , Hematoma/sangre , Hematoma/complicaciones , Anciano , Anciano de 80 o más Años , Hemorragia Cerebral/diagnóstico por imagen , Estudios de Cohortes , Femenino , Hematoma/diagnóstico por imagen , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neuroimagen , Factores de Riesgo

RESUMEN

Carotid stenosis involves narrowing of the lumen in the carotid artery potentially leading to a stroke, which is the third leading cause of death in the United States. Several recent investigations have found that plaque structure and composition may represent a more direct biomarker of plaque rupture risk compared with the degree of stenosis. In this study, pulse wave imaging was applied in 111 (n = 11, N = 13 plaques) patients diagnosed with moderate (>50%) to severe (>80%) carotid artery stenosis to investigate the feasibility of characterizing plaque properties based on the pulse wave-induced arterial wall dynamics captured by pulse wave imaging. Five (n = 5 patients, N = 20 measurements) healthy volunteers were also imaged as a control group. Both conventional and high-frame-rate plane wave radiofrequency imaging sequences were used to generate piecewise maps of the pulse wave velocity (PWV) at a single depth along stenotic carotid segments, as well as intra-plaque PWV mapping at multiple depths. Intra-plaque cumulative displacement and strain maps were also calculated for each plaque region. The Bramwell-Hill equation was used to estimate the compliance of the plaque regions based on the PWV and diameter. Qualitatively, wave convergence, elevated PWV and decreased cumulative displacement around and/or within regions of atherosclerotic plaque were observed and may serve as biomarkers for plaque characterization. Intra-plaque mapping revealed the potential to capture wave reflections between calcified inclusions and differentiate stable (i.e., calcified) from vulnerable (i.e., lipid) plaque components based on the intra-plaque PWV and cumulative strain. Quantitatively, one-way analysis of variance indicated that the pulse wave-induced cumulative strain was significantly lower (p < 0.01) in the moderately and severely calcified plaques compared with the normal controls. As expected, compliance was also significantly lower in the severely calcified plaques regions compared with the normal controls (p < 0.01). The results from this pilot study indicated the potential of pulse wave imaging coupled with strain imaging to differentiate plaques of varying stiffness, location and composition. Such findings may serve as valuable information to compensate for the limitations of currently used methods for the assessment of stroke risk.

Asunto(s)

Estenosis Carotídea/diagnóstico por imagen , Análisis de la Onda del Pulso/métodos , Ultrasonografía/métodos , Adulto , Anciano , Arterias Carótidas/diagnóstico por imagen , Femenino , Humanos , Masculino , Proyectos Piloto