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Targeting myeloid cells, especially microglia, for the treatment of neuroinflammatory diseases such as multiple sclerosis (MS), is underappreciated. Our in silico drug screening reveals topoisomerase 1 (TOP1) inhibitors as promising drug candidates for microglial modulation. We show that TOP1 is highly expressed in neuroinflammatory conditions, and TOP1 inhibition using camptothecin (CPT) and its FDA-approved analog topotecan (TPT) reduces inflammatory responses in microglia/macrophages and ameliorates neuroinflammation in vivo. Transcriptomic analyses of sorted microglia from LPS-challenged mice reveal an altered transcriptional phenotype following TPT treatment. To target myeloid cells, we design a nanosystem using ß-glucan-coated DNA origami (MyloGami) loaded with TPT (TopoGami). MyloGami shows enhanced specificity to myeloid cells while preventing the degradation of the DNA origami scaffold. Myeloid-specific TOP1 inhibition using TopoGami significantly suppresses the inflammatory response in microglia and mitigates MS-like disease progression. Our findings suggest that TOP1 inhibition in myeloid cells represents a therapeutic strategy for neuroinflammatory diseases and that the myeloid-specific nanosystems we designed may also benefit the treatment of other diseases with dysfunctional myeloid cells.
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Enfermedades Neuroinflamatorias , Inhibidores de Topoisomerasa I , Animales , ADN , Macrófagos , Ratones , Inhibidores de Topoisomerasa I/farmacología , Topotecan/farmacologíaRESUMEN
BACKGROUND: This study aimed to validate apparent diffusion coefficient (ADC) values and thresholds to predict poor neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors by quantitatively analysing the ADC values via brain magnetic resonance imaging (MRI). METHODS: This observational study used prospectively collected data from two tertiary academic hospitals. The derivation cohort comprised 70% of the patients randomly selected from one hospital, whereas the internal validation cohort comprised the remaining 30%. The external validation cohort used the data from another hospital, and the MRI data were restricted to scans conducted at 3 T within 72-96 h after an OHCA experience. We analysed the percentage of brain volume below a specific ADC value at 50-step intervals ranging from 200 to 1200 × 10-6 mm2/s, identifying thresholds that differentiate between good and poor outcomes. Poor neurological outcomes were defined as cerebral performance categories 3-5, 6 months after experiencing an OHCA. RESULTS: A total of 448 brain MRI scans were evaluated, including a derivation cohort (n = 224) and internal/external validation cohorts (n = 96/128, respectively). The proportion of brain volume with ADC values below 450, 500, 550, 600, and 650 × 10-6 mm2/s demonstrated good to excellent performance in predicting poor neurological outcomes in the derivation group (area under the curve [AUC] 0.89-0.91), and there were no statistically significant differences in performances among the derivation, internal validation, and external validation groups (all P > 0.5). Among these, the proportion of brain volume with an ADC below 600 × 10-6 mm2/s predicted a poor outcome with a 0% false-positive rate (FPR) and 76% (95% confidence interval [CI] 68-83) sensitivity at a threshold of > 13.2% in the derivation cohort. In both the internal and external validation cohorts, when using the same threshold, a specificity of 100% corresponded to sensitivities of 71% (95% CI 58-81) and 78% (95% CI 66-87), respectively. CONCLUSIONS: In this validation study, by consistently restricting the MRI types and timing during quantitative analysis of ADC values in brain MRI, we observed high reproducibility and sensitivity at a 0% FPR. Prospective multicentre studies are necessary to validate these findings.
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Paro Cardíaco Extrahospitalario , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Paro Cardíaco Extrahospitalario/diagnóstico por imagen , Estudios Prospectivos , Pronóstico , Sobrevivientes/estadística & datos numéricos , Estudios de Cohortes , Imagen por Resonancia Magnética/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Valor Predictivo de las Pruebas , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatologíaRESUMEN
BACKGROUND: To determine if the density distribution proportion of Hounsfield unit (HUdp) in head computed tomography (HCT) images can be used to quantitatively measure cerebral edema in survivors of out-of-hospital cardiac arrest (OHCA). METHODS: This retrospective observational study included adult comatose OHCA survivors who underwent HCT within 6 h (first) and 72-96 h (second), all performed using the same CT scanner. Semi-automated quantitative analysis was used to identify differences in HUdp at specific HU ranges across the intracranial component based on neurological outcome. Cerebral edema was defined as the increased displacement of the sum of HUdp values (ΔHUdp) at a specific range between two HCT scans. Poor neurological outcome was defined as cerebral performance categories 3-5 at 6 months after OHCA. RESULTS: Twenty-three (42%) out of 55 patients had poor neurological outcome. Significant HUdp differences were observed between good and poor neurological outcomes in the second HCT scan at HU = 1-14, 23-35, and 39-56 (all P < 0.05). Only the ΔHUdp = 23-35 range showed a significant increase and correlation in the poor neurological outcome group (4.90 vs. -0.72, P < 0.001) with the sum of decreases in the other two ranges (r = 0.97, P < 0.001). Multivariate logistic regression analysis demonstrated a significant association between ΔHUdp = 23-35 range and poor neurological outcomes (adjusted OR, 1.12; 95% CI: 1.02-1.24; P = 0.02). CONCLUSION: In this cohort study, the increased displacement in ΔHUdp = 23-35 range is independently associated with poor neurological outcome and provides a quantitative assessment of cerebral edema formation in OHCA survivors.
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Edema Encefálico , Paro Cardíaco Extrahospitalario , Adulto , Humanos , Edema Encefálico/etiología , Edema Encefálico/complicaciones , Estudios de Cohortes , Pronóstico , Paro Cardíaco Extrahospitalario/diagnóstico por imagen , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/complicaciones , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos , SobrevivientesRESUMEN
BACKGROUND: This study aimed to investigate the association between ultra-early (within 6 h after return of spontaneous circulation [ROSC]) brain diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological outcomes in comatose survivors after out-of-hospital cardiac arrest. METHODS: We conducted a registry-based observational study from May 2018 to February 2022 at a Chungnam national university hospital in Daejeon, Korea. Presence of high-signal intensity (HSI) (PHSI) was defined as a HSI on DW-MRI with corresponding hypoattenuation on the apparent diffusion coefficient map irrespective of volume after hypoxic ischemic brain injury; absence of HSI was defined as AHSI. The primary outcome was the dichotomized cerebral performance category (CPC) at 6 months, defined as good (CPC 1-2) or poor (CPC 3-5). RESULTS: Of the 110 patients (30 women [27.3%]; median (interquartile range [IQR]) age, 58 [38-69] years), 48 (43.6%) had a good neurological outcome, time from ROSC to MRI scan was 2.8 h (IQR 2.0-4.0 h), and the PHSI on DW-MRI was observed in 46 (41.8%) patients. No patients in the PHSI group had a good neurological outcome compared with 48 (75%) patients in the AHSI group. In the AHSI group, cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels were significantly lower in the group with good neurological outcome compared to the group with poor neurological outcome (20.1 [14.4-30.7] ng/mL vs. 84.3 [32.4-167.0] ng/mL, P < 0.001). The area under the curve for PHSI on DW-MRI was 0.87 (95% confidence interval [CI] 0.80-0.93), and the specificity and sensitivity for predicting a poor neurological outcome were 100% (95% CI 91.2%-100%) and 74.2% (95% CI 62.0-83.5%), respectively. A higher sensitivity was observed when CSF NSE levels were combined (88.7% [95% CI 77.1-95.1%]; 100% specificity). CONCLUSIONS: In this cohort study, PHSI findings on ultra-early DW-MRI were associated with poor neurological outcomes 6 months following the cardiac arrest. The combined CSF NSE levels showed higher sensitivity at 100% specificity than on DW-MRI alone. Prospective multicenter studies are required to confirm these results.
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Paro Cardíaco Extrahospitalario , Femenino , Humanos , Persona de Mediana Edad , Encéfalo , Estudios de Cohortes , Imagen de Difusión por Resonancia Magnética/métodos , Paro Cardíaco Extrahospitalario/complicaciones , Paro Cardíaco Extrahospitalario/diagnóstico por imagen , Fosfopiruvato Hidratasa , Pronóstico , Estudios Prospectivos , Masculino , Adulto , AncianoRESUMEN
BACKGROUND: This study aimed to quantitatively analyse ultra-early brain diffusion-weighted magnetic resonance imaging (DW-MRI) findings to determine the apparent diffusion coefficient (ADC) threshold associated with neurological outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA). METHODS: This retrospective study included adult survivors of comatose OHCA who underwent DW-MRI imaging scans using a 3-T MRI scanner within 6 h of the return of spontaneous circulation (ROSC). We investigated the association between neurological outcomes and ADC values obtained through voxel-based analysis on DW-MRI. Additionally, we constructed multivariable logistic regression models with pupillary light reflex (PLR), serum neuron-specific enolase (NSE), and ADC values as independent variables to predict poor neurological outcomes. The primary outcome was poor neurological outcome 6 months after ROSC, determined by the Cerebral Performance Category 3-5. RESULTS: Overall, 131 patients (26% female) were analysed, of whom 74 (57%) showed poor neurological outcomes. The group with a poor neurological outcome had lower mean whole brain ADC values (739.1 vs. 787.1 × 10-6 mm/s) and higher percentages of voxels with ADC below threshold in all ranges (250-1150) (all P < 0.001). The mean whole brain ADC values (area under the receiver operating characteristic curve [AUC] 0.83) and the percentage of voxels with ADC below 600 (AUC 0.81) had the highest sensitivity of 51% (95% confidence interval [CI] 39.4-63.1; cut-off value ≤ 739.2 × 10-6 mm2/s and > 17.2%, respectively) when the false positive rate (FPR) was 0%. In the multivariable model, which also included PLR, NSE, and mean whole brain ADC values, poor neurological outcome was predicted with the highest accuracy (AUC 0.91; 51% sensitivity). This model showed more accurate prediction and sensitivity at an FPR of 0% than did the combination of PLR and NSE (AUC 0.86; 30% sensitivity; P = 0.03). CONCLUSIONS: In this cohort study, early voxel-based quantitative ADC analysis after ROSC was associated with poor neurological outcomes 6 months after cardiac arrest. The mean whole brain ADC value demonstrated the highest sensitivity when the FPR was 0%, and including it in the multivariable model improved the prediction of poor neurological outcomes.
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Paro Cardíaco Extrahospitalario , Adulto , Humanos , Femenino , Masculino , Paro Cardíaco Extrahospitalario/complicaciones , Paro Cardíaco Extrahospitalario/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Coma , Estudios de Cohortes , Estudios Retrospectivos , Pronóstico , SobrevivientesRESUMEN
BACKGROUND: Early prediction of brain death (BD) after the return of spontaneous circulation (ROSC) in patients with cardiac arrest would be useful for the proper distribution of good quality transplantable organs and medical resources. We aimed to early identify independent risk factors of BD and their predictive performance in out-of-hospital cardiac arrest (OHCA) survivors. METHODS: This retrospective observational study included adult OHCA survivors from May 2018 to February 2021. Independent risk factors for progression to BD were identified by performing multivariate logistic regression analysis, including clinical, laboratory, biological parameters and prognostic factors, obtained within 6 h after ROSC. Neuron-specific enolase (NSE) level were categorized into quartile. The primary outcome was BD occurrence. RESULTS: Overall, 108 patients were included in this analysis, 31 (29%) of whom had BD. In multivariate logistic regression analysis, initial serum NSE levels in the fourth quartile compared to the first quartile (odds ratio [OR], 88.5; 95% confidence interval [CI]: 7.0-1113.6) and absence of pupil light reflex (PLR) (OR, 40.3; 95% CI: 3.8-430.3) were independently associated with BD. According to the receiver operating characteristic curve analysis, initial serum NSE levels and PLR showed good-to-excellent and fair-to-good prognostic performance, respectively (area under the curve [AUC], 0.90; 95% CI: 0.83-0.95 vs. 0.81; 95% CI: 0.72-0.88). Additionally, the combination of both the risk factors (AUC, 0.96; 95% CI: 0.90-0.99) showed significantly higher predictive performance for BD than when using them individually (P = 0.04 and P < 0.01, respectively). CONCLUSION: High levels of initial serum NSE and PLR obtained within 6 h after ROSC may help early predict progression to BD in OHCA survivors. A large prospective multicenter study should be conducted to confirm these results.
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Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario , Adulto , Muerte Encefálica , Humanos , Paro Cardíaco Extrahospitalario/complicaciones , Fosfopiruvato Hidratasa , Pronóstico , Estudios Prospectivos , Factores de Riesgo , SobrevivientesRESUMEN
BACKGROUND: The use of personal protective equipment for respiratory infection control during cardiopulmonary resuscitation (CPR) is a physical burden to healthcare providers. The duration for which CPR quality according to recommended guidelines can be maintained under these circumstances is important. We investigated whether a 2-min shift was appropriate for chest compression and determined the duration for which chest compression was maintained in accordance with the recommended guidelines while wearing personal protective equipment. METHODS: This prospective crossover simulation study was performed at a single center from September 2020 to October 2020. Five indicators of CPR quality were measured during the first and second sessions of the study period. All participants wore a Level D powered air-purifying respirator (PAPR), and the experiment was conducted using a Resusci Anne manikin, which can measure the quality of chest compressions. Each participant conducted two sessions. In Session 1, the sequence of 2 min of chest compressions, followed by a 2-min rest, was repeated twice; in Session 2, the sequence of 1-min chest compressions followed by a 1-min rest was repeated four times. RESULTS: All 34 participants completed the study. The sufficiently deep compression rate was 65.9 ± 31.1% in the 1-min shift group and 61.5 ± 30.5% in the 2-min shift group. The mean compression depth was 52.8 ± 4.3 mm in the 1-min shift group and 51.0 ± 6.1 mm in the 2-min shift group. These two parameters were significantly different between the two groups. There was no significant difference in the other values related to CPR quality. CONCLUSIONS: Our findings indicated that 1 min of chest compressions with a 1-min rest maintained a better quality of CPR while wearing a PAPR.
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Reanimación Cardiopulmonar/educación , Personal de Salud/educación , Masaje Cardíaco/métodos , Dispositivos de Protección Respiratoria , Adulto , Competencia Clínica , Estudios Cruzados , Femenino , Humanos , Control de Infecciones , Masculino , Maniquíes , Estudios Prospectivos , Control de Calidad , República de Corea , DescansoRESUMEN
PURPOSE: This study aimed to determine whether the blood urea nitrogen to serum albumin (B/A) ratio is a useful prognostic factor of mortality in patients with aspiration pneumonia. METHODS: The study included patients with aspiration pneumonia who had been admitted to our hospital via the emergency department (ED) between January 1, 2014 and December 31, 2018. The 28-day mortality after the ED visits was the primary end point of this study. The data of the survivors and non-survivors were compared. RESULTS: A final diagnosis of aspiration pneumonia was made for 443 patients during the study period. Significant differences were observed in age, respiratory rate, albumin levels, total protein levels, blood urea nitrogen levels, C-reactive protein levels, glucose, and Charlson comorbidity index scores between the survivor and non-survivor groups. Moreover, the B/A ratio was significantly higher in the non-survivor group than that in the survivor group. The area under the curve for the B/A ratio was 0.70 [95% confidence interval (CI) 0.65-0.74], 0.71 for the PSI (95% CI 0.67-0.76), 0.64 for CURB-65 (95% CI 0.60-0.69), and 0.65 for albumin (95% CI 0.60-0.70) on the receiver operating characteristic curve for predicting mortality within 28 days of the ED visit. Multivariable logistic regression analysis revealed that the B/A ratio (>7, OR 3.40, 95% CI 1.87-6.21, P < 0.001) was associated with mortality within 28 days of the ED visit. CONCLUSION: The B/A ratio is a simple and potentially useful prognostic factor of mortality in aspiration pneumonia patients.
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Nitrógeno de la Urea Sanguínea , Neumonía por Aspiración/mortalidad , Albúmina Sérica/análisis , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Neumonía por Aspiración/sangre , Neumonía por Aspiración/diagnóstico , Curva ROC , Estudios RetrospectivosRESUMEN
BACKGROUND/OBJECTIVE: Cerebrospinal fluid (CSF) and serum lactate levels were assessed to predict poor neurologic outcome 3 months after return of spontaneous circulation (ROSC). We compared arterio-CSF differences in the lactate (ACDL) levels between two neurologic outcome groups. METHODS: This retrospective observational study involved out-of-hospital cardiac arrest (OHCA) survivors who had undergone target temperature management. CSF and serum samples were obtained immediately (lactate0), and at 24 (lactate24), 48 (lactate48), and 72 (lactate72) h after ROSC, and ACDL was calculated at each time point. The primary outcome was poor 3-month neurologic outcome (cerebral performance categories 3-5). RESULTS: Of 45 patients, 27 (60.0%) showed poor neurologic outcome. At each time point, CSF lactate levels were significantly higher in the poor neurologic outcome group than in the good neurologic outcome group (6.97 vs. 3.37, 4.20 vs. 2.10, 3.50 vs. 2.00, and 2.79 vs. 2.06, respectively; all P < 0.05). CSF lactate's prognostic performance was higher than serum lactate at each time point, and lactate24 showed the highest AUC values (0.89, 95% confidence interval, 0.75-0.97). Over time, ACDL decreased from - 1.30 (- 2.70-0.77) to - 1.70 (- 3.2 to - 0.57) in the poor neurologic outcome group and increased from - 1.22 (- 2.42-0.32) to - 0.64 (- 2.31-0.15) in the good neurologic outcome group. CONCLUSIONS: At each time point, CSF lactate showed better prognostic performance than serum lactate. CSF lactate24 showed the highest prognostic performance for 3-month poor neurologic outcome. Over time, ACDL decreased in the poor neurologic outcome group and increased in the good neurologic outcome group.
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Hipotermia Inducida , Paro Cardíaco Extrahospitalario , Encéfalo , Humanos , Ácido Láctico , Paro Cardíaco Extrahospitalario/terapia , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: This study aimed to assess the global impairment and prognostic performance of cerebral perfusions (CP) measured by dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) in out-of-hospital cardiac arrest (OHCA) patients after sustained restoration of spontaneous circulation (ROSC). MATERIALS AND METHODS: This is a single-centre, prospective observational study. OHCA patients performed DSC-PWI within 8â¯h after ROSC were enrolled. We quantified the CP parameters, such as cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), time to peak (TTP), and time to maximum of the residue function (Tmax) either by normalization or arterial input function (AIF). The primary and secondary outcomes were survival to discharge and comparison of prognostic performance between CP parameters and serum neuron-specific enolase (NSE) using area under the receiver operating characteristic (AUROC) and sensitivity values. RESULTS: Thirty-one patients were included in this study. CBV and TTP quantified by normalization, and MTT and Tmax quantified by AIF showed significantly higher CP values in the non-survival group (pâ¯=â¯0.02, 0.03, 0.02, and <0.01, respectively). Their AUROCs and 100% specific sensitivities were 0.74/25.0%, 0.60/33.3%, 0.75/56.3%, and 0.79/43.8%, respectively. MTT quantified by AIF showed sensitivity in predicting mortality at an early stage of PCA care, comparable with NSE. CONCLUSION: Hyperaemia and delayed CP were generally observed in OHCA patients regardless of outcomes. MTT and Tmax quantified by AIF have prognostic performance in predicting mortality, comparable with NSE. Further prospective multicentre studies are required to confirm our results.
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Paro Cardíaco Extrahospitalario , Circulación Cerebrovascular , Humanos , Angiografía por Resonancia Magnética , Paro Cardíaco Extrahospitalario/diagnóstico por imagen , Perfusión , SobrevivientesRESUMEN
Background and Objectives: The coronavirus infection 2019 (COVID-19) pandemic has affected emergency department (ED) management. Its viral transmission necessitates the use of isolation rooms and personal protective equipment for treating suspected patients, such as those with fever. This delays the time until the first encounter with the patients, thereby increasing the length of stay (LOS) in the ED. We aimed to compare delays in the ED LOS and clinical processes between the COVID-19 period and pre-COVID-19 period. Moreover, we intended to evaluate if the aforementioned delay affected patient outcomes. Materials and Methods: We conducted a single-center, retrospective study in Korea. Patients with fever were compared between the "COVID-19 period" from March 2020 to August 2020 and the "pre-COVID-19 period" from March 2019 to September 2019. We compared the overall ED LOS and individual time variable, including initial diagnostic tests (laboratory tests, radiography), specific diagnostic test (computed tomography), and treatment processes (antibiotics). A logistic regression analysis was conducted to identify the association between hospital admission and patient data. Results: We enrolled 931 and 749 patients during pre- and COVID-19 periods, respectively. Patients with fever remained in the ED for a longer duration during the COVID-19 period (pre-COVID-19:207.7 ± 102.7 min vs. during COVID-19: 223.5 ± 119.4 min, p = 0.004). The total time for performing laboratory tests and radiography displayed significant differences between the two periods, particularly from the time of patient arrival in the ED to the time of issuing the order. The time until antibiotic administration was delayed in the COVID-19 period (pre-COVID-19:195.8 ± 103.3 min vs. during COVID-19: 216.9 ± 108.4 min, p = 0.003). The logistic regression analysis for hospital admission identified ED LOS as an independent factor in both periods. Conclusions: The delay until encountering patients with fever resulted in longer ED LOS during the COVID-19 period; however, it possibly did not increase the hospital admission rates.
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COVID-19 , Brotes de Enfermedades , Servicio de Urgencia en Hospital , Humanos , Tiempo de Internación , Pandemias , Estudios Retrospectivos , SARS-CoV-2RESUMEN
PURPOSE: We evaluated whether combining the serum albumin level and the Prediction Rule for Admission policy in Complicated urinary Tract InfeCtion LEiden (PRACTICE) class could be a prognostic predictor in elderly patients with urinary tract infection (UTI). METHODS: We retrospectively included adult patients (age ≥ 65 years) with UTI who were hospitalized in the emergency department (ED) between January 1, 2014 and December 31, 2018. We graded the serum albumin level and classified the PRACTICE score; the modified PRACTICE was defined as the sum of the albumin level grade and the PRACTICE class. We comparatively assessed the predictive value for in-hospital mortality and admission to the intensive care unit (ICU) in survivor and non-survivor groups. RESULTS: In total, the study analysis included 1159 patients, and in-hospital mortality was 3.4% (n = 39). The modified PRACTICE score (4.0 [1.4] vs 6.1 [1.2], p < 0.001) was significantly increased in the non-survivor group. The area under the curve value of factors associated with in-hospital mortality were the Modified Early Warning Score (MEWS) 0.57 (95% CI 0.54-0.60), albumin 0.83 (95% CI 0.81-0.85), PRACTICE 0.71 (95% CI 0.69-0.74), and the modified PRACTICE 0.86 (95% CI 0.84-0.88). Factors associated with ICU admission were MEWS 0.65 (95% CI 0.62-0.68), albumin 0.66 (95% CI 0.64-0.69), PRACTICE 0.66 (95% CI 0.63-0.68), and the modified PRACTICE 0.72 (95% CI 0.69-0.74). CONCLUSION: The modified PRACTICE score can be a useful prognostic predictor in elderly patients with UTI.
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Geriatría/instrumentación , Pronóstico , Albúmina Sérica/análisis , Infecciones Urinarias/complicaciones , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores/análisis , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Servicio de Urgencia en Hospital/organización & administración , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Geriatría/métodos , Geriatría/normas , Humanos , Masculino , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Análisis de Supervivencia , Infecciones Urinarias/sangre , Infecciones Urinarias/diagnósticoRESUMEN
BACKGROUND: Serum interleukin-6 (IL-6) is a cytokine released in response to an inflammatory stimulus or tissue injury. IL-6 levels are known to increase in patients with brain injury. OBJECTIVE: We investigated the neurologic outcomes associated with serum IL-6 levels in out-of-hospital cardiac arrest (OHCA) survivors who underwent target temperature management (TTM). METHODS: This was a prospective single-center observational study from October 2018 to November 2019 in a cohort of 45 patients. Serum inflammatory markers (IL-6, C-reactive protein, white blood cells) were determined in samples obtained immediately and at 24, 48, and 72 h after the return of spontaneous circulation (ROSC). Poor neurologic outcome, defined as Cerebral Performance Category 3-5 at 3 months after cardiac arrest, was the primary outcome. RESULTS: Among 45 patients enrolled in this study, 25 (55.6%) patients showed a poor neurologic outcome. IL-6 levels were significantly higher in the poor neurologic outcome group immediately (IL-60) after ROSC. The area under the curve (AUC) value of IL-60 was the highest among those of serum IL-6, CRP, and WBC at each time point. The IL-6 levels for predicting poor neurologic outcome had a sensitivity of 75.0%, with 80% specificity at IL-60. The AUC of IL-60 was 0.810 (95% confidence interval 0.664-0.913), with a cutoff value of 346.7 pg mL-1. CONCLUSIONS: Serum IL-6 level immediately after ROSC was a highly specific and sensitive marker for the 3-month poor neurologic outcome, and may be a useful early predictive marker of neurologic outcome in OHCA survivors treated with TTM.
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Hipotermia Inducida , Paro Cardíaco Extrahospitalario , Humanos , Interleucina-6 , Paro Cardíaco Extrahospitalario/terapia , Pronóstico , Estudios Prospectivos , Sobrevivientes , TemperaturaRESUMEN
PURPOSE: The technical factors which improve cosmetic outcomes and which need to be emphasized in education of junior residents have yet to be described. We compared cases in which suturing was performed by either junior emergency medicine residents or experts, in order to determine the focus of future education and training. METHODS: Wound registry data was reviewed and retrospectively analyzed from September 2015 to February 2016. Only patients who visited the emergency room with facial lacerations were enrolled, and their wound registry data sheets were reviewed. Practitioners were divided into junior resident and expert groups. We assessed the progress using the Stony Brook Scar Evaluation Scale (SBSES) 5-10â¯days following suturing. RESULTS: Sixty-six patients were enrolled; 43 (65.2%) were men. The median (interquartile range) cosmetic scores (SBSES scale) for suturing performed by junior residents or experts were 3 (2-4) and 5 (4-5), respectively (pâ¯=â¯0.001). The percentage of maximum scores for each SBSES category was significantly lower in the junior resident group than in the expert group for width (68% vs. 86%), hatch marks (68% vs. 93%), and overall appearance (41% vs. 80%) (all pâ¯<â¯0.001). CONCLUSIONS: There were significant differences in scar widths and hatch marks, which were attributable to the skill level of the practitioner who performed the suturing of facial lacerations. Junior residents should be educated about maintenance of proper tension, atraumatic technique, and performing appropriate trimming or debridement.
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Cicatriz/prevención & control , Traumatismos Faciales/cirugía , Internado y Residencia , Laceraciones/cirugía , Técnicas de Sutura/educación , Adulto , Anciano , Competencia Clínica , Desbridamiento/educación , Medicina de Emergencia/educación , Servicio de Urgencia en Hospital/estadística & datos numéricos , Traumatismos Faciales/patología , Femenino , Humanos , Laceraciones/patología , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios RetrospectivosRESUMEN
PURPOSE: A suture line placed with the same direction as the relaxed skin tension line leads to good healing, but a suture line with over 30 degrees of angle from the relaxed skin tension line leads to longer healing time and more prominent scarring. W-plasty is widely used to change the direction of the scar or to divide it into several split scars. In this study, we applied W-plasty to patients with facial lacerations in the emergency department. METHODS: From June 2012 to December 2014, 35 patients underwent simple repair or W-plasty for facial lacerations. Patients in the simple repair group underwent resection following a thermal margin, and the W-plasty group was resected within a pre-designed margin of W-shaped laceration. We assessed prognosis using the Stony Brook Scar Evaluation Scale (SBSES) after 10 days (short-term) and six months (long-term), respectively, following suture removal. RESULTS: Among 35 patients, 15 (42.9%) underwent simple debridement and 20 (57.1%) underwent W-plasty. In the W-plasty group, there was no difference between short-term and long-term follow-up showing high SBSES, but in the simple debridement group, long-term follow-up SBSES significantly decreased. W-plasty SBSES was higher than simple debridement at short-term as well as long-term follow-up. CONCLUSION: We experienced good results of direct W-plasty application at six-month long-term follow-up. Therefore, W-plasty application is more effective in reducing scar appearance than a simple debridement method for facial laceration patients with an angle of 30 degrees or more to the relaxed skin tension line.
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Cicatriz/prevención & control , Contractura/prevención & control , Desbridamiento/métodos , Procedimientos Quirúrgicos Dermatologicos , Traumatismos Faciales/cirugía , Laceraciones/cirugía , Adulto , Cicatriz/patología , Cicatriz/psicología , Contractura/patología , Contractura/psicología , Procedimientos Quirúrgicos Dermatologicos/métodos , Estética , Traumatismos Faciales/patología , Traumatismos Faciales/psicología , Femenino , Estudios de Seguimiento , Humanos , Laceraciones/patología , Masculino , Persona de Mediana Edad , Satisfacción del Paciente/estadística & datos numéricos , República de Corea/epidemiología , Estudios Retrospectivos , Técnicas de Sutura , Cicatrización de HeridasRESUMEN
Traumatic tattoos can result from the accidental deposition of foreign particles in the dermis. These pigmented particles can become permanently lodged in the dermis after wound re-epithelialization and lead to irregular black or blue skin discoloration. Different methods exist for tattoo removal. The best strategy is to prevent traumatic tattoo formation by immediately removing the foreign particles before the healing process begins. Here, we present a fine-tuned, hydrosurgical debridement system to selectively debride wounds and preserve as much viable tissue as possible.
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Desbridamiento/métodos , Cuerpos Extraños/cirugía , Trastornos de la Pigmentación/prevención & control , Piel/lesiones , Accidentes de Tránsito , Niño , Servicio de Urgencia en Hospital , Cuerpos Extraños/patología , Humanos , Masculino , Piel/patologíaRESUMEN
Bee sting is one of the most commonly encountered insect bites in the world. Despite the common occurrence of local and systemic allergic reactions, there are few reports of ischemic stroke after bee stings. To the best our knowledge, there have been no reports on involuntary hyperkinetic movement disorders after multiple bee stings. We report the case of a 50-year-old man who developed involuntary movements of the left leg 24 hours after multiple bee stings, and the cause was confirmed to be a right temporal infarction on a diffusion magnetic resonance imaging scan. Thus, we concluded that the involuntary movement disorder was caused by right temporal infarction that occurred after multiple bee stings.
Asunto(s)
Infarto Cerebral/etiología , Discinesias/etiología , Mordeduras y Picaduras de Insectos/complicaciones , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Infarto Cerebral/diagnóstico , Imagen de Difusión por Resonancia Magnética , Servicio de Urgencia en Hospital , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Neuroimagen , Lóbulo Temporal/irrigación sanguínea , Tomografía Computarizada por Rayos XRESUMEN
The pathophysiology of ALS involves many signs of a disruption in copper homeostasis, with both excess free levels and functional deficiency likely occurring simultaneously. This is crucial, as many important physiological functions are performed by cuproenzymes. While it is unsurprising that many ALS symptoms are related to signs of copper deficiency, resulting in vascular, antioxidant system and mitochondrial oxidative respiration deficiencies, there are also signs of copper toxicity such as ROS generation and enhanced protein aggregation. We discuss how copper also plays a key role in proteostasis and interacts either directly or indirectly with many of the key aggregate-prone proteins implicated in ALS, such as TDP-43, C9ORF72, SOD1 and FUS as well as the effect of their aggregation on copper homeostasis. We suggest that loss of cuproprotein function is at the core of ALS pathology, a condition that is driven by a combination of unbound copper and ROS that can either initiate and/or accelerate protein aggregation. This could trigger a positive feedback cycle whereby protein aggregates trigger the aggregation of other proteins in a chain reaction that eventually captures elements of the proteostatic mechanisms in place to counteract them. The end result is an abundance of aggregated non-functional cuproproteins and chaperones alongside depleted intracellular copper stores, resulting in a general lack of cuproenzyme function. We then discuss the possible aetiology of ALS and illustrate how strong risk factors including environmental toxins such as BMAA and heavy metals can functionally behave to promote protein aggregation and disturb copper metabolism that likely drives this vicious cycle in sporadic ALS. From this synthesis, we propose restoration of copper balance using copper delivery agents in combination with chaperones/chaperone mimetics, perhaps in conjunction with the neuroprotective amino acid serine, as a promising strategy in the treatment of this incurable disease.
RESUMEN
Common features of neurodegenerative diseases are oxidative and inflammatory imbalances as well as the misfolding of proteins. An excess of free metal ions can be pathological and contribute to cell death, but only copper and zinc strongly promote protein aggregation. Herein we demonstrate that the endogenous copper-binding tripeptide glycyl-l-histidyl-l-lysine (GHK) has the ability to bind to and reduce copper redox activity and to prevent copper- and zinc-induced cell death in vitro. In addition, GHK prevents copper- and zinc-induced bovine serum albumin aggregation and reverses aggregation through resolubilizing the protein. We further demonstrate the enhanced toxicity of copper during inflammation and the ability of GHK to attenuate this toxicity. Finally, we investigated the effects of copper on enhancing paraquat toxicity and report a protective effect of GHK. We therefore conclude that GHK has potential as a cytoprotective compound with regard to copper and zinc toxicity, with positive effects on protein solubility and aggregation that warrant further investigation in the treatment of neurodegenerative diseases.
Asunto(s)
Muerte Celular , Cobre , Oligopéptidos , Agregado de Proteínas , Zinc , Cobre/farmacología , Cobre/química , Cobre/metabolismo , Zinc/farmacología , Zinc/química , Zinc/metabolismo , Agregado de Proteínas/efectos de los fármacos , Animales , Oligopéptidos/farmacología , Oligopéptidos/química , Muerte Celular/efectos de los fármacos , Humanos , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/metabolismoRESUMEN
BACKGROUND: This study aimed to explore the changes in blood-brain barrier (BBB) permeability and intracranial pressure (ICP) for the first 24 h after the return of spontaneous circulation (ROSC) and their association with injury severity of cardiac arrest. METHODS: This prospective study analysed the BBB permeability assessed using the albumin quotient (Qa) and ICP every 2 h for the first 24 h after ROSC. The injury severity of cardiac arrest was assessed using Pittsburgh Cardiac Arrest Category (PCAC) scores. The primary outcome was the time course of changes in the BBB permeability and ICP for the first 24 h after ROSC and their association with injury severity (PCAC scores of 1-4). RESULTS: Qa and ICP were measured 274 and 197 times, respectively, in 32 enrolled patients. Overall, the BBB permeability increased progressively over time after ROSC, and then it increased significantly at 18 h after ROSC compared with the baseline. In contrast, the ICP revealed non-significant changes for the first 24 h after ROSC. The Qa in the PCAC 2 group was < 0.01, indicating normal or mild BBB disruption at all time points, whereas the PCAC 3 and 4 groups showed a significant increase in BBB permeability at 14 and 22 h, and 12 and 14 h after ROSC, respectively. CONCLUSION: BBB permeability increased progressively over time for the first 24 h after ROSC despite post-resuscitation care, whereas ICP did not change over time. BBB permeability has an individual pattern when stratified by injury severity.