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1.
Pediatr Emerg Care ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38471759

RESUMO

OBJECTIVE: Pediatric sepsis screening is becoming the standard of care for children presenting to the emergency department (ED) and has been shown to improve recognition of severe sepsis, but it is unknown if these screening tools can predict progression of disease. The objective of this study was to determine if any elements of a sepsis triage trigger tool were predictive of progression to hypotensive shock in children presenting to the ED with fever and tachycardia. METHODS: This study is a retrospective case-control study of children ≤18 years presenting to an ED with fever and tachycardia, comparing those who went on to develop hypotensive shock in the subsequent 24 hours (case) to those who did not (control). Primary outcome was the proportion of encounters where the patient had specific abnormal vital signs or clinical signs as components of the sepsis triage score. The secondary outcomes were the proportion of encounters where the patient had a sepsis risk factor. RESULTS: During the study period, there were 94 patients who met case criteria and 186 controls selected. In the adjusted multivariable model, the 2 components of the sepsis triage score that were more common in case patients were the presence of severe cerebral palsy (adjusted odds ratio, 9.4 [3.7, 23.9]) and abnormal capillary refill at triage (adjusted odds ratio, 3.1 [1.4, 6.9]). CONCLUSIONS: Among children who present to a pediatric ED with fever and tachycardia, those with prolonged capillary refill at triage or severe cerebral palsy were more likely to progress to decompensated septic shock, despite routine ED care.

2.
Ann Emerg Med ; 83(6): 568-575, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38363279

RESUMO

Most children in the United States present to community hospitals for emergency department (ED) care. Those who are acutely ill and require critical care are stabilized and transferred to a tertiary pediatric hospital with intensive care capabilities. During the fall of 2022 "tripledemic," with a marked increase in viral burden, there was a nationwide surge in pediatric ED patient volume. This caused ED crowding and decreased availability of pediatric hospital intensive care beds across the United States. As a result, there was an inability to transfer patients who were critically ill out, and the need for prolonged management increased at the community hospital level. We describe the experience of a Massachusetts community ED during this surge, including the large influx in pediatric patients, the increase in those requiring critical care, and the total number of critical care hours as compared with the same time period (September to December) in 2021. To combat these challenges, the pediatric ED leadership applied a disaster management framework based on the 4 S's of space, staff, stuff, and structure. We worked collaboratively with general emergency medicine leadership, nursing, respiratory therapy, pharmacy, local clinicians, our regional health care coalition, and emergency medical services (EMS) to create and implement the pediatric surge strategy. Here, we present the disaster framework strategy, the interventions employed, and the barriers and facilitators for implementation in our community hospital setting, which could be applied to other community hospital facing similar challenges.


Assuntos
COVID-19 , Serviço Hospitalar de Emergência , Hospitais Comunitários , Humanos , Hospitais Comunitários/organização & administração , Serviço Hospitalar de Emergência/organização & administração , Massachusetts , Criança , COVID-19/epidemiologia , Hospitais Pediátricos/organização & administração , Planejamento em Desastres/organização & administração , Capacidade de Resposta ante Emergências , Cuidados Críticos/organização & administração , SARS-CoV-2 , Aglomeração , Estudos de Casos Organizacionais
3.
J Pediatr ; 263: 113718, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37659590

RESUMO

OBJECTIVES: To compare the outcomes of pediatric severe sepsis and septic shock among patients with culture-positive and culture-negative sepsis and to determine if there are differentiating markers of disease severity between these 2 populations during their initial presentation and emergency department (ED) stay. STUDY DESIGN: Retrospective cohort study of patients ≤21 years of age who presented to the ED of a single children's hospital with severe sepsis or septic shock from June 1, 2017 to June 5, 2019. RESULTS: There were 235 patients who met criteria for severe sepsis or septic shock. Of these, 139 (59.1%) had culture-negative sepsis and 96 (40.9%) had culture-positive sepsis. In the adjusted multivariable model, children with culture-negative sepsis had more intensive care unit (ICU)-free days than those with culture-positive sepsis (27.3 vs 24.1; adjusted median differences [aMD] -2.6 [-4.4, -0.8]). There were no differences in mortality or hospital-free days. On initial presentation, there were no differences in fever, hypothermia, tachycardia, tachypnea, or hypotension between the 2 groups. There were no differences in proportion of patients receiving the following interventions: intravenous (IV) antibiotics, IV fluids, vasoactive medications, CPR, intubation, or time from arrival to provision of these interventions. CONCLUSIONS: Culture-negative sepsis constitutes a substantial proportion of pediatric severe sepsis and septic shock. In this study, patients with culture-negative and culture-positive sepsis presented similarly on arrival to the ED and received similar treatments while there. Patients with culture-negative sepsis had more ICU-free days than those with culture-positive sepsis, although differences in hospital length of stay (LOS) and mortality were not observed.


Assuntos
Sepse , Choque Séptico , Humanos , Criança , Choque Séptico/diagnóstico , Choque Séptico/terapia , Estudos Retrospectivos , Sepse/diagnóstico , Sepse/terapia , Tempo de Internação , Unidades de Terapia Intensiva , Serviço Hospitalar de Emergência , Mortalidade Hospitalar
4.
Clin Pediatr (Phila) ; 62(5): 474-480, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36401509

RESUMO

To determine whether a lack of response to antipyretics was associated with bacteremia, we performed a cross-sectional study involving children with an initial temperature ≥38°C presenting to a pediatric emergency department (ED) from 2012 to 2020 who received an antipyretic and had a blood culture obtained. We assessed the association of resolution of fever at specific time points after antipyretic administration with bacteremia adjusting for age, complex chronic condition, blood culture source, type of antipyretic, and height of temperature. Among 6319 febrile children, 242 (3.8%) had bacteremia. The adjusted odds ratio of bacteremia was 1.6 (95% confidence interval: 1.2-2.2) among children who remained febrile at 180 minutes and 1.7 (1.2-2.4) among children who remained febrile at 240 minutes. Among febrile children presenting to a tertiary care ED for whom a blood culture was obtained, the response to an antipyretic varies based on the presence or absence of bacteremia.


Assuntos
Antipiréticos , Bacteriemia , Febre , Febre/tratamento farmacológico , Febre/etiologia , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Serviço Hospitalar de Emergência , Antipiréticos/uso terapêutico , Pediatria , Humanos , Masculino , Feminino , Pré-Escolar , Criança , Estudos Transversais , Lactente
6.
Am J Emerg Med ; 57: 234.e1-234.e2, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35430099

RESUMO

Lyme disease is the most frequently reported vector-borne illness in the United States. It is caused by infection with Borrelia burgdorferi via the bite of an infected blacklegged tick (Ixodes spp.) Lyme disease has three stages: early localized, early disseminated, and late. Early disseminated Lyme disease may include neurologic manifestations such as cranial nerve palsy, meningitis, and radicular pain (also called radiculoneuritis). Isolated radiculoneuritis is a rare presentation of early disseminated Lyme disease and is likely underrecognized. We report a case of isolated Lyme radiculoneuritis in a child in Massachusetts characterized by fever and allodynia of the upper back that was treated in the emergency department. Laboratory investigation demonstrated elevated inflammatory markers and positive Lyme testing. Magnetic resonance imaging with gadolinium contrast revealed nerve root enhancement in C5-C6 and C6-C7. The symptoms resolved with oral doxycycline. Neuropathic pain should raise suspicion for neurologic manifestations of Lyme disease in North America even in the absence of meningitis and cranial nerve palsy. We report how timely recognition of this rare syndrome in North America is important and may prevent progression to late disease.


Assuntos
Borrelia burgdorferi , Doenças dos Nervos Cranianos , Síndrome de Guillain-Barré , Doença de Lyme , Meningite , Criança , Doenças dos Nervos Cranianos/etiologia , Síndrome de Guillain-Barré/complicações , Humanos , Doença de Lyme/complicações , Doença de Lyme/diagnóstico , Doença de Lyme/tratamento farmacológico , Meningite/complicações , América do Norte
7.
Clin Pract Cases Emerg Med ; 6(1): 91-92, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35226861

RESUMO

CASE PRESENTATION: An eight-week-old infant presented to the emergency department with two weeks of fluctuating swelling and erythema of her right upper eyelid. On examination, she had swelling of the right upper eyelid with ptosis and proptosis as well as a nevus simplex on the upper eyelid. Orbital magnetic resonance imaging demonstrated a proliferating orbital hemangioma. DISCUSSION: Periorbital erythema and swelling are often infectious or allergic, but in infants with a fluctuating course, underlying vascular malformation must be considered. Without early provider recognition, periocular hemangiomas have the potential to cause vision-related complications.

8.
Clin Imaging ; 82: 156-160, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34844100

RESUMO

INTRODUCTION: Medical centers have dramatically increased the use of magnetic resonance imaging (MRI). At 2 large academic tertiary care centers in New York City, nearly half of inpatient MRI orders took more than 12 h to complete, delaying patient discharge and increasing avoidable hospital days. We posited that transitioning inpatient MRIs to outpatient facilities, when safe and appropriate, could reduce inpatient MRI orders and avoidable hospital days. METHODS: We manually reviewed 59 inpatient MRI orders delayed on the estimated date of discharge (EDD). These orders were often delayed due to no standard process to escalate orders for medical reasons or no system to coordinate outpatient orders. We developed a revised workflow involving an automation platform that flagged inpatient MRI orders requested within 24 h of the EDD and emailed the care team to request a second review of the order. The care team reconsidered whether the order was (1) required for discharge, (2) non-urgent and could be converted to an outpatient order, or (3) unnecessary and could be canceled. RESULTS: Over 9 months, the automation platform flagged 618 inpatient MRI orders, of which 53.9% (333/618) were reviewed by the care team. Among the orders, 24.0% (80/333) of reviewed orders and 12.9% (80/618) of all orders were transitioned to either outpatient or canceled orders. These transitioned orders were associated with 267 fewer avoidable hospital days and a cost savings of $199,194. CONCLUSION: A standardized process and second review of inpatient MRI orders on the EDD can reduce inappropriate orders and more effectively use inpatient imaging resources. PRECIS: A standardized workflow and automation platform encouraged a second review of inpatient MRI orders to reduce inappropriate orders, avoidable hospital days, and hospital costs.


Assuntos
Pacientes Internados , Pacientes Ambulatoriais , Hospitais , Humanos , Imageamento por Ressonância Magnética , Fluxo de Trabalho
9.
Am J Emerg Med ; 51: 53-57, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34673476

RESUMO

OBJECTIVE: Understanding differences in mortality rate secondary to sepsis between pediatric and general emergency departments (EDs) would help identify strategies to improve pediatric sepsis care. We aimed to determine if pediatric sepsis mortality differs between pediatric and general EDs. METHODS: We performed a nationally representative, retrospective cohort study using the 2008-2017 Nationwide Emergency Department Sample (NEDS) to examine visits by patients less than 19 years old with a diagnostic code of severe sepsis or septic shock. We generated national estimates of study outcomes using NEDS survey weights. We compared pediatric to general EDs on the outcomes of ED mortality and hospital mortality. We determined adjusted mortality risk using logistic regression, controlling for age, gender, complex care code, and geographic region. RESULTS: There were 54,129 weighted pediatric ED visits during the study period with a diagnosis code of severe sepsis or septic shock. Of these visits, 285 died in the ED (0.58%) and 5065 died during their hospital stay (9.8%). Mortality risk prior to ED disposition in pediatric and general EDs was 0.31% and 0.72%, respectively (adjusted odds ratio (aOR), 95% confidence interval (CI): 0.36 (0.14-0.93)). Mortality risk prior to hospital discharge in pediatric and general EDs was 7.5% and 10.9%, respectively (aOR, 95% CI: 0.55 (0.41-0.72)). CONCLUSIONS: In a nationally representative sample, pediatric mortality from severe sepsis or septic shock was lower in pediatric EDs than in general EDs. Identifying features of pediatric ED care associated with improved sepsis mortality could translate into improved survival for children wherever they present with sepsis.


Assuntos
Sepse/mortalidade , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Serviço Hospitalar de Emergência , Feminino , Mortalidade Hospitalar , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Análise Multivariada , Estudos Retrospectivos , Sepse/terapia , Taxa de Sobrevida , Estados Unidos/epidemiologia
11.
Am J Emerg Med ; 50: 778-783, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34879502

RESUMO

OBJECTIVE: To identify the association between readily available laboratory biomarkers and the development of severe sepsis in children presenting to the emergency department (ED) with systemic inflammatory response syndrome (SIRS). METHODS: In this retrospective cohort study, ED patient encounters from June 2018 to June 2019 that triggered an automated sepsis alert based on SIRS criteria were analyzed. Encounters were included if the patient had any of the following laboratory tests sent within 6 h of ED arrival: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactic acid, and procalcitonin. For each of the biomarkers, a receiver operating characteristic (ROC) curve was created for our primary outcome, severe sepsis within 24 h of ED disposition, and our secondary outcome, severe sepsis with a positive bacterial culture. For each ROC curve, we calculated the area under the curve (AUC) with 95% confidence intervals (95% CI) and created cutoff points to achieve 90% sensitivity and 90% sensitivity for the primary and secondary outcomes. RESULTS: During the study period, 4349/61,195 (7.1%) encounters triggered an automated sepsis alert. Of those, 1207/4349 (27.8%) had one of the candidate biomarkers sent within 6 h of ED arrival and were included in the study. A total of 100/1207 (8.3%) met criteria for severe sepsis within 24 h of arrival, and 41/100 severe sepsis cases (41%) were deemed culture-positive. Procalcitonin had the highest AUC for identifying severe sepsis [0.62 (95% CI 0.52-0.73)] while ESR and CRP had the highest AUC for culture-positive sepsis [0.68 (95% CI 0.47-0.89) and 0.67 (95% CI 0.53-0.81), respectively]. At 90% sensitivity for detecting severe sepsis, all of the biomarker threshold values fell within that laboratory test's normal range. At 90% specificity for severe sepsis, threshold values were as follows: procalcitonin 2.72 ng/mL, CRP 16.79 mg/dL, ESR 79.5 mm/h and lactic acid 3.6 mmol/L. CONCLUSION: Our data indicate that CRP, ESR, lactic acid, and procalcitonin elevations were all specific, but not sensitive, in identifying children in the ED with SIRS who go on to develop severe sepsis.


Assuntos
Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Regras de Decisão Clínica , Ácido Láctico/sangue , Pró-Calcitonina/sangue , Sepse/diagnóstico , Adolescente , Área Sob a Curva , Biomarcadores/sangue , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidade do Paciente , Curva ROC , Estudos Retrospectivos , Sepse/sangue , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico
12.
JBJS Case Connect ; 11(2)2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33974600

RESUMO

CASE: A 16-year-old football player presented with chronic ACL deficiency along with bicompartmental bucket handle meniscal tears. CONCLUSION: We present a "triple cruciate" sign in addition to the triple posterior cruciate ligament (PCL) sign seen on Magnetic Resonance Imaging (MRI) to aid in diagnosing this injury.


Assuntos
Futebol Americano , Ligamento Cruzado Posterior , Lesões do Menisco Tibial , Adolescente , Artroscopia , Humanos , Imageamento por Ressonância Magnética , Ligamento Cruzado Posterior/diagnóstico por imagem , Ligamento Cruzado Posterior/cirurgia , Lesões do Menisco Tibial/diagnóstico por imagem , Lesões do Menisco Tibial/patologia , Lesões do Menisco Tibial/cirurgia
14.
J Pediatr ; 231: 193-199.e1, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33358842

RESUMO

OBJECTIVES: To determine if implementation of an automated sepsis screening algorithm with low positive predictive value led to inappropriate resource utilization in emergency department (ED) patients as evidenced by an increased proportion of children with false-positive sepsis screens receiving intravenous (IV) antibiotics. STUDY DESIGN: Retrospective cohort study comparing children <18 years of age presenting to an ED who triggered a false-positive sepsis alert during 2 different 5-month time periods: a silent alert period when alerts were generated but not visible to clinicians and an active alert period when alerts were visible. Primary outcome was the proportion of patients who received IV antibiotics. Secondary outcomes included proportion receiving IV fluid boluses, proportion admitted to the hospital, and ED length of stay (LOS). RESULTS: Of 1457 patients, 1277 triggered a false-positive sepsis alert in the silent and active alert periods, respectively. In multivariable models, there were no changes in the proportion administered IV antibiotics (27.0% vs 27.6%, aOR 1.1 [0.9,1.3]) or IV fluid boluses (29.7% vs 29.1%, aOR 1.0 [0.8,1.2]). Differences in ED LOS and proportion admitted to the hospital were not significant when controlling for similar changes seen across all ED encounters. CONCLUSIONS: An automated sepsis screening algorithm did not lead to changes in the proportion receiving IV antibiotics or IV fluid boluses, department LOS, or the proportion admitted to the hospital for patients with false-positive sepsis alerts.


Assuntos
Algoritmos , Antibacterianos/uso terapêutico , Sepse/diagnóstico , Sepse/tratamento farmacológico , Criança , Pré-Escolar , Estudos de Coortes , Registros Eletrônicos de Saúde , Serviço Hospitalar de Emergência , Reações Falso-Positivas , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Tempo de Internação/estatística & dados numéricos , Masculino , Estudos Retrospectivos
15.
Fam Pract ; 38(1): 38-42, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32667977

RESUMO

BACKGROUND: Primary care is the ideal place to implement behaviour change interventions for weight management. However, most primary care physicians are not managing patient weight as a standard of care due to lack of knowledge, skills and reimbursement. Generating more physicians who are familiar and comfortable with providing weight management is essential in leveraging a global change. In our university free clinic, medical students provide healthy lifestyle counselling using shared decision making to each patient at every clinic visit. OBJECTIVE: Improve the efficacy of behaviour change interventions via increased patient responsiveness and adherence. METHODS: The needs assessment demonstrated a subpar patient response rate to check-ins regarding behavioural change goals. In the first and second interventions, check-in message structure and contact schedule were varied to maximize patient responsiveness and goal achievement. RESULTS: In the needs assessment, 58% of patients responded to follow-ups and 58% of patients accomplished their goal. The first intervention cycle resulted in an improvement of responsiveness to 70% and accomplishment of goals to 59%. The second intervention cycle resulted in an improvement of responsiveness to 78% and accomplishment of goals to 74%. CONCLUSIONS: Messages that were frequent, unique, succinct and delivered within 4 weeks after the clinic visit resulted in the highest response rate and goal attainment. Other primary care clinics can use these interventions to increase patient completion of implemented behaviour changes for a healthier lifestyle.


Assuntos
Clínica Dirigida por Estudantes , Redução de Peso , Peso Corporal , Estilo de Vida Saudável , Humanos , Estudantes
16.
J Surg Educ ; 78(1): 178-200, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32591323

RESUMO

OBJECTIVE: To query the literature for predictive factors for performance on arthroscopic and laparoscopic surgical simulators in novice surgical trainees. These predictive factors may prove a valuable tool in identifying certain innate potential to becoming a future skilled surgeon that could benefit both surgical residency candidates and program directors alike, while also improving patient care. DESIGN: Systematic Review. RESULTS: The initial searches yielded 249 articles. After screening titles/abstracts and implementing inclusion and exclusion criteria, 36 studies were included in the final systematic review. CONCLUSIONS: Current literature suggests that video game experience/frequency, psychomotor and visuospatial aptitude, and perceptual ability are among the most promising predictive indicators of baseline simulator performance. Study limitations include utilization of different standards for characterizing predictive factors. Future studies should aim to utilize standard guidelines for accurate quantification of innate predictive factors. Future research should also focus on utilizing standardized simulator platforms and aptitude tests to allow for more accurate cross-study comparisons and meta-analyses with larger sample sizes.


Assuntos
Internato e Residência , Laparoscopia , Artroscopia , Competência Clínica , Simulação por Computador , Humanos
17.
Arthrosc Sports Med Rehabil ; 2(6): e829-e837, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33376998

RESUMO

PURPOSE: The purpose of this study was to analyze the effects of past participation in athletics, the playing of musical instruments and video games and other variables on medical students' performance on an arthroscopic simulator task as well as other assessments of visuospatial ability. METHODS: We assessed 50 medical students by using previously validated tests of manual dexterity and spatial reasoning as well as performance on an arthroscopic surgical simulator. Inclusion criteria were to be 18 years of age or older and to be a student studying in the M.D. program at a single public state university. Exclusion criteria were previous use of an arthroscopic surgery training device or active participation in an actual arthroscopic surgery, defined as participating as a surgeon, resident trainee, physician's assistant, or other similarly credentialed professional. Students were also assessed by the use of a high-fidelity ultrasound simulator as a marker of visuospatial capacity. Students were then surveyed about lifestyle characteristics and personal attributes hypothesized to predict surgical skill, such as playing sports, instruments or video games. RESULTS: A total of 49 participants were included in this study. High levels of athletic experience were significantly associated with improved performance on the arthroscopic surgical simulator (P = .008). Participants with higher levels of athletic experience were more likely to achieve competence on the arthroscopic surgical simulator (P = .006). Scores on the arthroscopic simulator task were significantly correlated with both ultrasound simulator shape-identification task scores and masked mirror-tracing task scores, as independent measures of visuospatial ability (P = .015 and P = .013, respectively). CONCLUSIONS: This study provides evidence of a statistically significant correlation between increased experience in athletics and single-use test performance on an arthroscopic surgical simulator. Subjects who reported higher levels of experience in athletics were significantly more likely to achieve competence in the arthroscopic surgical simulator task. Finally, statistically significant correlations were found between subjects' performance scores on tasks assessed by the surgical simulator, masked mirror-trace assessment and ultrasound simulator. CLINICAL RELEVANCE: Simulator-based training and education allow for the development of arthroscopic skills prior to operating on a live patient in a clinical situation. This is an area of great interest in orthopaedic education. Our study evaluates parameters in a trainee that may relate to a higher performance level in technical skills on an arthroscopic surgical simulator.

18.
Int J Stroke ; 13(1): 11-23, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28920538

RESUMO

Background Intraventricular hemorrhage is a significant cause of mortality and morbidity worldwide. Treating intraventricular hemorrhage with intraventricular fibrinolytic therapy via a catheter is becoming an increasingly utilized intervention. Aims This meta-analysis aimed to investigate the role of intraventricular fibrinolytic treatment in hypertensive intraventricular hemorrhage patients and evaluate the effect sizes for survival as well as level of function at differing time points. Summary of review PubMed, CNKI, VIP, and Wanfang were searched using the terms "IVH" and "IVH and ICH" for human studies with adult patients published between January 1950 and July 2016. Seventeen publications were selected. Data analysis showed lower rates of mortality in the treatment group at 30 days ( P < 0.001), 180 days ( P = 0.001), 365 days ( P = 0.40), and overall ( P < 0.001). Pooling modified Rankin Scale and Glasgow outcome scale data, the treatment group had more good functional outcomes at 30 days ( P = 0.38), 90 days ( P = 0.04), 180 days ( P = 0.31), 365 days ( P = 0.76), and overall ( P = 0.02). Good functional outcome was defined as modified Rankin Scale score of 0 to 3 or a Glasgow outcome scale score of 3 to 5. Conclusions Intraventricular fibrinolytic for treatment of hypertensive intraventricular hemorrhage reduces mortality and potentially leads to an increased number of good functional outcomes. Different functional outcome scales (modified Rankin Scale or Glasgow outcome scale) produce different effect sizes. Intraventricular fibrinolytic treatment may offer intraventricular hemorrhage patients a targeted therapy that produces meaningful mortality benefit and possible functional outcome benefits.


Assuntos
Hemorragia Cerebral Intraventricular/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Hemorragia Cerebral Intraventricular/mortalidade , Humanos , Resultado do Tratamento
19.
Infect Immun ; 81(3): 713-22, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23264053

RESUMO

Clostridium difficile infection (CDI) results in toxin-induced epithelial injury and marked intestinal inflammation. Fecal markers of intestinal inflammation correlate with CDI disease severity, but regulation of the inflammatory response is poorly understood. Previous studies demonstrated that C. difficile toxin TcdA activates p38 kinase in tissue culture cells and mouse ilium, resulting in interleukin-8 (IL-8) release. Here, we investigated the role of phosphorylated mitogen-activated protein kinase (MAPK)-activated protein kinase (MK2 kinase, pMK2), a key mediator of p38-dependent inflammation, in CDI. Exposure of cultured intestinal epithelial cells to the C. difficile toxins TcdA and TcdB resulted in p38-dependent MK2 activation. Toxin-induced IL-8 and GROα release required MK2 activity. We found that p38 and MK2 are activated in response to other actin-disrupting agents, suggesting that toxin-induced cytoskeleton disruption is the trigger for kinase-dependent cytokine response. Phosphorylated MK2 was detected in the intestines of C. difficile-infected hamsters and mice, demonstrating for the first time that the pathway is activated in infected animals. Furthermore, we found that elevated pMK2 correlated with the presence of toxigenic C. difficile among 100 patient stool samples submitted for C. difficile testing. In conclusion, we find that MK2 kinase is activated by TcdA and TcdB and regulates the expression of proinflammatory cytokines. Activation of p38-MK2 in infected animals and humans suggests that this pathway is a key driver of intestinal inflammation in patients with CDI.


Assuntos
Clostridioides difficile , Infecções por Clostridium/metabolismo , Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Biomarcadores , Linhagem Celular Tumoral , Infecções por Clostridium/microbiologia , Infecções por Clostridium/patologia , Colo/microbiologia , Colo/patologia , Cricetinae , Citocinas/química , Citocinas/genética , Citocinas/metabolismo , Fezes/química , Humanos , Inflamação/microbiologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
20.
PLoS One ; 6(4): e19098, 2011 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-21544204

RESUMO

Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI), the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ∼40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum.


Assuntos
Receptores de IgE/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina E/metabolismo , Ligação Proteica/genética , Isoformas de Proteínas/sangue , Isoformas de Proteínas/metabolismo , Receptores de IgE/metabolismo
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