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1.
J Nurs Adm ; 54(4): 220-226, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38501847

RESUMEN

In response to high nurse turnover, a 12-hospital health system team created a sustainable, formalized, and interprofessional mentoring model to improve nurse retention. In the 1st year of the program, 506 mentor-mentee matches were made, and nearly 5000 hours of mentoring time were logged. Data revealed that turnover was significantly reduced in both the mentor and mentee groups compared with employees who were not in the program.


Asunto(s)
Tutoría , Mentores , Humanos , Evaluación de Programas y Proyectos de Salud
2.
BMC Med Ethics ; 23(1): 45, 2022 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-35439950

RESUMEN

BACKGROUND: Commentators believe that the ethical decision-making climate is instrumental in enhancing interprofessional collaboration in intensive care units (ICUs). Our aim was twofold: (1) to determine the perception of the ethical climate, levels of moral distress, and intention to leave one's job among nurses and physicians, and between the different ICU types and (2) determine the association between the ethical climate, moral distress, and intention to leave. METHODS: We performed a cross-sectional questionnaire study between May 2021 and August 2021 involving 206 nurses and physicians in a large urban academic hospital. We used the validated Ethical Decision-Making Climate Questionnaire (EDMCQ) and the Measure of Moral Distress for Healthcare Professionals (MMD-HP) tools and asked respondents their intention to leave their jobs. We also made comparisons between the different ICU types. We used Pearson's correlation coefficient to identify statistically significant associations between the Ethical Climate, Moral Distress, and Intention to Leave. RESULTS: Nurses perceived the ethical climate for decision-making as less favorable than physicians (p < 0.05). They also had significantly greater levels of moral distress and higher intention to leave their job rates than physicians. Regarding the ICU types, the Neonatal/Pediatric unit had a significantly higher overall ethical climate score than the Medical and Surgical units (3.54 ± 0.66 vs. 3.43 ± 0.81 vs. 3.30 ± 0.69; respectively; both p ≤ 0.05) and also demonstrated lower moral distress scores (both p < 0.05) and lower "intention to leave" scores compared with both the Medical and Surgical units. The ethical climate and moral distress scores were negatively correlated (r = -0.58, p < 0.001); moral distress and "intention to leave" was positively correlated (r = 0.52, p < 0.001); and ethical climate and "intention to leave" were negatively correlated (r = -0.50, p < 0.001). CONCLUSIONS: Significant differences exist in the perception of the ethical climate, levels of moral distress, and intention to leave between nurses and physicians and between the different ICU types. Inspecting the individual factors of the ethical climate and moral distress tools can help hospital leadership target organizational factors that improve interprofessional collaboration, lessening moral distress, decreasing turnover, and improved patient care.


Asunto(s)
Actitud del Personal de Salud , Intención , Niño , Estudios Transversales , Hospitales , Humanos , Recién Nacido , Unidades de Cuidados Intensivos , Satisfacción en el Trabajo , Principios Morales , Estrés Psicológico , Encuestas y Cuestionarios
3.
J Immunol ; 202(8): 2240-2253, 2019 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-30796179

RESUMEN

Alpha-1 antitrypsin (AAT) is an acute phase protein that possesses immune-regulatory and anti-inflammatory functions independent of antiprotease activity. AAT deficiency (AATD) is associated with early-onset emphysema and chronic obstructive pulmonary disease. Of interest are the AATD nonsense mutations (termed null or Q0), the majority of which arise from premature termination codons in the mRNA coding region. We have recently demonstrated that plasma from an AATD patient homozygous for the Null Bolton allele (Q0bolton ) contains AAT protein of truncated size. Although the potential to alleviate the phenotypic consequences of AATD by increasing levels of truncated protein holds therapeutic promise, protein functionality is key. The goal of this study was to evaluate the structural features and anti-inflammatory capacity of Q0bolton-AAT. A low-abundance, truncated AAT protein was confirmed in plasma of a Q0bolton-AATD patient and was secreted by patient-derived induced pluripotent stem cell-hepatic cells. Functional assays confirmed the ability of purified Q0bolton-AAT protein to bind neutrophil elastase and to inhibit protease activity. Q0bolton-AAT bound IL-8 and leukotriene B4, comparable to healthy control M-AAT, and significantly decreased leukotriene B4-induced neutrophil adhesion (p = 0.04). Through a mechanism involving increased mRNA stability (p = 0.007), ataluren treatment of HEK-293 significantly increased Q0bolton-AAT mRNA expression (p = 0.03) and Q0bolton-AAT truncated protein secretion (p = 0.04). Results support the rationale for treatment with pharmacological agents that augment levels of functional Q0bolton-AAT protein, thus offering a potential therapeutic option for AATD patients with rare mutations of similar theratype.


Asunto(s)
Alelos , Codón sin Sentido , Deficiencia de alfa 1-Antitripsina , alfa 1-Antitripsina , Adulto , Femenino , Humanos , Células Madre Pluripotentes Inducidas/inmunología , Células Madre Pluripotentes Inducidas/metabolismo , Hígado/inmunología , Hígado/metabolismo , Masculino , alfa 1-Antitripsina/sangre , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/inmunología , Deficiencia de alfa 1-Antitripsina/sangre , Deficiencia de alfa 1-Antitripsina/genética , Deficiencia de alfa 1-Antitripsina/inmunología
4.
Thorax ; 75(4): 321-330, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31959730

RESUMEN

INTRODUCTION: Alpha-1 antitrypsin (AAT) deficiency (AATD) is associated with early onset emphysema. The aim of this study was to investigate whether AAT binding to plasma constituents could regulate their activation, and in AATD, exploit this binding event to better understand the condition and uncover novel biomarkers of therapeutic efficacy. METHODS: To isolate AAT linker proteins, plasma samples were separated by size exclusion chromatography, followed by co-immunoprecipitation. AAT binding proteins were identified by mass spectrometry. Complement turnover and activation was determined by ELISA measurement of C3, C3a and C3d levels in plasma of healthy controls (n=15), AATD (n=51), non-AATD patients with obstructive airway disease (n=10) and AATD patients post AAT augmentation therapy (n=5). RESULTS: Direct binding of complement C3 to AAT was identified in vivo and in vitro. Compared with healthy controls, a breakdown product of C3, C3d, was increased in AATD (0.04 µg/mL vs 1.96 µg/mL, p=0.0002), with a significant correlation between radiographic pulmonary emphysema and plasma levels of C3d (R2=0.37, p=0.001). In vivo, AAT augmentation therapy significantly reduced plasma levels of C3d in comparison to patients not receiving AAT therapy (0.15 µg/mL vs 2.18 µg/mL, respectively, p=0.001). DISCUSSION: Results highlight the immune-modulatory impact of AAT on the complement system, involving an important potential role for complement activation in disease pathogenesis in AATD. The association between plasma C3d levels and pulmonary disease severity, that decrease in response to AAT augmentation therapy, supports the exploration of C3d as a candidate biomarker of therapeutic efficacy in AATD.


Asunto(s)
Complemento C3/metabolismo , Enfisema Pulmonar/epidemiología , Trastornos Respiratorios/epidemiología , Deficiencia de alfa 1-Antitripsina/epidemiología , Deficiencia de alfa 1-Antitripsina/terapia , alfa 1-Antitripsina/uso terapéutico , Anciano , Análisis de Varianza , Biomarcadores/sangre , Western Blotting , Estudios de Casos y Controles , Comorbilidad , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Masculino , Espectrometría de Masas/métodos , Persona de Mediana Edad , Enfisema Pulmonar/sangre , Enfisema Pulmonar/diagnóstico , Valores de Referencia , Trastornos Respiratorios/sangre , Trastornos Respiratorios/diagnóstico , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Resultado del Tratamiento , Deficiencia de alfa 1-Antitripsina/diagnóstico
5.
Eur Respir J ; 55(4)2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32060059

RESUMEN

Obstructive pulmonary disease in patients with α1 antitrypsin (AAT) deficiency (AATD) occurs earlier in life compared with patients without AATD. To understand this further, the aim of this study was to investigate whether AATD presents with altered neutrophil characteristics, due to the specific lack of plasma AAT, compared with non-AATD COPD.This study focussed on the neutrophil plasma membrane and, by use of label-free tandem mass spectrometry, the proteome of the neutrophil membrane was compared in forced expiratory volume in 1 s (FEV1)-matched AATD, non-AATD COPD and in AATD patients receiving weekly AAT augmentation therapy (n=6 patients per cohort). Altered protein expression in AATD was confirmed by Western blot, ELISA and fluorescence resonance energy transfer analysis.The neutrophil membrane proteome in AATD differed significantly from that of COPD as demonstrated by increased abundance and activity of primary granule proteins including neutrophil elastase on the cell surface in AATD. The signalling mechanism underlying increased degranulation involved Rac2 activation, subsequently resulting in proteinase-activated receptor 2 activation by serine proteinases and enhanced reactive oxygen species production. In vitro and ex vivo, AAT reduced primary granule release and the described plasma membrane variance was resolved post-AAT augmentation therapy in vivo, the effects of which significantly altered the AATD neutrophil membrane proteome to that of a non-AATD COPD cell.These results provide strong insight into the mechanism of neutrophil driven airways disease associated with AATD. Therapeutic AAT augmentation modified the membrane proteome to that of a typical COPD cell, with implications for clinical practice.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Deficiencia de alfa 1-Antitripsina , Volumen Espiratorio Forzado , Humanos , Neutrófilos , Proteoma , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Pruebas de Función Respiratoria , alfa 1-Antitripsina , Deficiencia de alfa 1-Antitripsina/tratamiento farmacológico
6.
J Trauma Nurs ; 21(4): 160-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25023839

RESUMEN

The relationship of burnout (BO), compassion fatigue (CF), compassion satisfaction (CS), and secondary traumatic stress (STS) to personal/environmental characteristics, coping mechanisms, and exposure to traumatic events was explored in 128 trauma nurses. Of this sample, 35.9% had scores consistent with BO, 27.3% reported CF, 7% reported STS, and 78.9% had high CS scores. High BO and high CF scores predicted STS. Common characteristics correlating with BO, CF, and STS were negative coworker relationships, use of medicinals, and higher number of hours worked per shift. High CS correlated with greater strength of supports, higher participation in exercise, use of meditation, and positive coworker relationships. Caring for trauma patients may lead to BO, CF, and STS; identifying predictors of these can inform the development of interventions to mitigate or minimize BO, CF, and STS in trauma nurses.


Asunto(s)
Agotamiento Profesional/epidemiología , Desgaste por Empatía/epidemiología , Enfermería de Urgencia , Personal de Enfermería en Hospital/psicología , Satisfacción Personal , Adulto , Estudios Transversales , Femenino , Grupos Focales , Humanos , Masculino , Persona de Mediana Edad , Personal de Enfermería en Hospital/estadística & datos numéricos , Adulto Joven
7.
Crit Care Nurs Clin North Am ; 35(2): 119-128, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37127369

RESUMEN

Traumatic cervical spinal cord injury can cause significant neurologic disability. A cervical spine injury impacts not only the neurologic system but also numerous other organ systems of the body. This complex injury requires a systematic approach to assessment and care aimed at preventing, recognizing, and treating potentially devastating secondary spinal cord injury and multisystem complications. This article focuses on the pathophysiology, initial presentation, and treatment of cervical spinal cord injury by body system.


Asunto(s)
Médula Cervical , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/terapia
8.
J Trauma Acute Care Surg ; 92(5): 906-915, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35001020

RESUMEN

BACKGROUND: In 2016, the National Academies of Science, Engineering and Medicine called for the development of a National Trauma Research Action Plan. The Department of Defense funded the Coalition for National Trauma Research to generate a comprehensive research agenda spanning the continuum of trauma and burn care. Given the public health burden of injuries to the central nervous system, neurotrauma was one of 11 panels formed to address this recommendation with a gap analysis and generation of high-priority research questions. METHODS: We recruited interdisciplinary experts to identify gaps in the neurotrauma literature, generate research questions, and prioritize those questions using a consensus-driven Delphi survey approach. We conducted four Delphi rounds in which participants generated key research questions and then prioritized the importance of the questions on a 9-point Likert scale. Consensus was defined as 60% or greater of panelists agreeing on the priority category. We then coded research questions using an National Trauma Research Action Plan taxonomy of 118 research concepts, which were consistent across all 11 panels. RESULTS: Twenty-eight neurotrauma experts generated 675 research questions. Of these, 364 (53.9%) reached consensus, and 56 were determined to be high priority (15.4%), 303 were deemed to be medium priority (83.2%), and 5 were low priority (1.4%). The research topics were stratified into three groups-severe traumatic brain injury (TBI), mild TBI (mTBI), and spinal cord injury. The number of high-priority questions for each subtopic was 46 for severe TBI (19.7%), 3 for mTBI (4.3%) and 7 for SCI (11.7%). CONCLUSION: This Delphi gap analysis of neurotrauma research identified 56 high-priority research questions. There are clear areas of focus for severe TBI, mTBI, and spinal cord injury that will help guide investigators in future neurotrauma research. Funding agencies should consider these gaps when they prioritize future research. LEVEL OF EVIDENCE: Diagnostic Test or Criteria, Level IV.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Traumatismos de la Médula Espinal , Lesiones Traumáticas del Encéfalo/epidemiología , Lesiones Traumáticas del Encéfalo/terapia , Consenso , Humanos , Salud Pública , Proyectos de Investigación
9.
J Trauma ; 71(6): 1524-7, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22182863

RESUMEN

BACKGROUND: Induced hypothermia after cardiac arrest is an accepted neuroprotective strategy. However, its role in cardiac arrest during acute trauma care is not yet defined. To characterize recent experience with this technique at our center, we undertook a detailed chart review of acute trauma patients managed with induced hypothermia after cardiac arrest. PATIENTS: From Trauma Registry records, we identified all adult patients (older than 17 years) admitted to our Level I trauma center from July 1, 2008, through June 30, 2010, who experienced cardiac arrest during acute trauma care and were managed via our induced hypothermia protocol. This requires maintenance of core body temperature between 32°C and 34°C for 24 hours after arrest. Patient clinical records were then reviewed for selected factors. RESULTS: Six acute trauma patients (3 male and 3 female; median age, 53 years) with cardiac arrest managed per protocol were identified. All injuries were due to blunt impact, and five of six injuries were motor-vehicle-associated. Median Injury Severity Score was 27; median prearrest Glasgow Coma Scale (GCS) score was 15. One patient arrested prehospital and the other 5 in-hospital. Median duration of arrest was 8 minutes. All were comatose after arrest. One death occurred, in the patient with a prehospital cardiac arrest. Two patients were discharged to chronic care facilities with GCS11-tracheostomy; three were discharged to active rehabilitation care facilities with GCS score of 14 to 15. There were no obvious complications related to cooling. CONCLUSIONS: Mild induced hypothermia can be beneficial in a selected group of trauma patients after cardiac arrest. Prospective trials are needed to explore the effects of targeted temperature management on coagulation in this patient group.


Asunto(s)
Paro Cardíaco/etiología , Paro Cardíaco/terapia , Hipotermia Inducida/métodos , Heridas y Lesiones/complicaciones , Adulto , Anciano de 80 o más Años , Cuidados Críticos/métodos , Femenino , Estudios de Seguimiento , Escala de Coma de Glasgow , Paro Cardíaco/mortalidad , Mortalidad Hospitalaria/tendencias , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Traumatismo Múltiple/complicaciones , Traumatismo Múltiple/diagnóstico , Traumatismo Múltiple/mortalidad , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Muestreo , Tasa de Supervivencia , Centros Traumatológicos , Resultado del Tratamiento , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/mortalidad
10.
AACN Adv Crit Care ; 32(1): 29-50, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33725106

RESUMEN

Traumatic brain injury is a devastating, life-changing event in most cases. After the primary brain insult, it is helpful to use evidence-based monitoring techniques to guide implementation of essential interventions to minimize secondary injury and thereby improve patient outcomes. An update on multimodal neuromonitoring is provided in this narrative review, with discussion of tools and techniques currently used in the treatment of patients with brain injury. Neuroprotective treatments, from the well-studied targeted temperature management to new potential therapeutics under investigation, such as glyburide, also are presented.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/terapia , Cuidados Críticos , Humanos
11.
Neurocrit Care ; 13(1): 29-39, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20407933

RESUMEN

BACKGROUND: Traumatic injuries to the cervical spine cause significant disability. Much of the morbidity and mortality that occurs in patients afflicted with cervical spinal cord injury (SCI) occurs early after injury due to primary neurologic dysfunction, systemic inflammation, concomitant injuries, treatments to prevent and ameliorate secondary insults, and prolonged immobilization. This study was undertaken to determine the incidence of organ dysfunction and failure using validated measures: the Multiple Organ Dysfunction Score (MODS) and the Sequential Organ Failure Assessment (SOFA). We also sought to determine if certain patient or injury characteristics were associated with the development of organ dysfunction and failure. METHODS: All patients who sustained isolated blunt cervical SCIs admitted to the R Adams Cowley Shock Trauma Center over a 15-month period were identified. American Spinal Injury Association (ASIA) motor scores, ASIA impairment scale (AIS) scores, and level of injury were recorded. Admission, first daily, worst daily, and aggregate MOD and SOFA scores were assigned for each of six organ systems. A P < 0.05 was considered significant for all statistical tests. RESULTS: Of 1,028 patients admitted with blunt spine injuries between January, 2007 and March, 2008, 40 patients were identified with an isolated cervical SCI that required an ICU length of stay (LOS) >24 h. Organ failure of at least one organ system occurred in 75% of patients as calculated by MOD score and 85% of patients calculated using SOFA criteria. Multiple organ failure was found in 55% by MOD and 62.5% by SOFA scores. The most frequent system to fail was the cardiovascular system by aggregate MODS (84%), while the respiratory system was the most frequently failed system by aggregate SOFA criteria (70%). There was a strong inverse correlation between ASIA motor score and aggregate MODS and SOFA scores (r = -0.56, P = 0.0002 and r = -0.51, P = 0.0009). AIS was also found to be inversely correlated with the development of organ failure (r = -0.47, P = 0.002 and r = -0.45, P = 0.004) while anatomic level of injury was found to correlate poorly with the incidence of organ failure (r = -0.11, P = 0.5 and r = -0.10, P = 0.5). Only ASIA motor score was significantly associated with sum aggregate organ dysfunction scores when controlling for age and injury severity score (parameter estimate = -0.082, P = 0.0005 for MODS and parameter estimate = -0.057, P = 0.006 for SOFA). CONCLUSIONS: This study is the first to describe the incidence of organ dysfunction and failure in patients with isolated acute traumatic cervical SCI using validated organ system dysfunction scores. Respiratory, cardiovascular, neurologic, renal, hepatic, and hematologic dysfunction occurred commonly both on admission and over the ICU stay. Respiratory, cardiovascular, and neurologic failure were frequently found, while renal, hepatic, and hematologic failures were uncommon. Multiple organ failure occurred in the majority of patients. ASIA motor score and AIS were found to strongly correlate with the development of organ dysfunction and failure. Level of injury should be used with caution when describing the risk of complications and the need for medical interventions.


Asunto(s)
Insuficiencia Multiorgánica/etiología , Traumatismos de la Médula Espinal/complicaciones , Heridas no Penetrantes/complicaciones , Enfermedad Aguda , Adulto , Anciano , Vértebras Cervicales , Estudios de Cohortes , Técnicas y Procedimientos Diagnósticos , Femenino , Mortalidad Hospitalaria , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/epidemiología , Factores de Riesgo , Traumatismos de la Médula Espinal/mortalidad
12.
J Trauma Nurs ; 17(4): 191-200, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21157252

RESUMEN

The purpose of this study is to determine the incidence of secondary traumatic stress (STS) in nurses who primarily care for trauma patients. A demographic/behavioral survey and Penn Inventory to measure the presence of STS were distributed to 262 nurses in a level I trauma center. Relationships between STS and years of experience, coping strategies, and personal and environmental characteristics were examined. Response rate was 49%. The median Penn Inventory score was 17.5. Nine nurses (7%) scored 35 or more, reflecting STS. Those with STS had fewer years of nursing experience and in trauma nursing, were more likely to use medicinals, and had fewer and weaker support systems.


Asunto(s)
Adaptación Psicológica , Actitud del Personal de Salud , Agotamiento Profesional/psicología , Traumatismo Múltiple/enfermería , Personal de Enfermería en Hospital/psicología , Trastornos por Estrés Postraumático/psicología , Adulto , Agotamiento Profesional/epidemiología , Agotamiento Profesional/etiología , Agotamiento Profesional/prevención & control , Distribución de Chi-Cuadrado , Femenino , Ambiente de Instituciones de Salud , Humanos , Incidencia , Masculino , Maryland/epidemiología , Persona de Mediana Edad , Investigación Metodológica en Enfermería , Personal de Enfermería en Hospital/educación , Personal de Enfermería en Hospital/organización & administración , Exposición Profesional/efectos adversos , Exposición Profesional/prevención & control , Exposición Profesional/estadística & datos numéricos , Salud Laboral , Personalidad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Apoyo Social , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/etiología , Trastornos por Estrés Postraumático/prevención & control , Encuestas y Cuestionarios , Centros Traumatológicos
13.
Front Pharmacol ; 11: 1098, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32765284

RESUMEN

In people with cystic fibrosis (PWCF), inflammation with concurrent infection occurs from a young age and significantly influences lung disease progression. Studies indicate that neutrophils are important effector cells in the pathogenesis of CF and in the development of anti-neutrophil cytoplasmic autoantibodies (ANCA). ANCA specific for bactericidal permeability increasing protein (BPI-ANCA) are detected in people with CF, and correlate with infection with Pseudomonas aeruginosa. The aim of this study was to determine the signaling mechanism leading to increased BPI release by CF neutrophils, while identifying IgG class BPI-ANCA in CF airways samples as the cause for impaired antimicrobial activity of BPI against P. aeruginosa. Plasma and/or bronchoalveolar lavage fluid (BAL) was collected from PWCF (n = 40), CF receiving ivacaftor therapy (n = 10), non-CF patient cohorts (n = 7) and healthy controls (n = 38). Plasma and BAL BPI and BPI-ANCA were measured by ELISA and GTP-bound Rac2 detected using an in vitro assay. The antibacterial effect of all treatments tested was determined by colony forming units enumeration. Levels of BPI are significantly increased in plasma (p = 0.007) and BALF (p < 0.0001) of PWCF. The signaling mechanism leading to increased degranulation and exocytosis of BPI by CF neutrophils (p = 0.02) involved enhancement of Rac2 GTP-loading (p = 0.03). The full-length BPI protein was detectable in all CF BAL samples and patients displayed ANCA with BPI specificity. IgG class autoantibodies were purified from CF BAL complexed to BPI (n=5), with IgG autoantibody cross-linking of antigen preventing BPI induced P. aeruginosa killing (p < 0.0001). Results indicate that the immune-mediated diminished antimicrobial defense, attributed to anti-BPI-IgG, necessitates the formation of a drug/immune complex intermediate that can maintain cytotoxic effects of BPI towards Gram-negative pathogens, with the potential to transform the current treatment of CF airways disease.

14.
Front Immunol ; 11: 600033, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33391268

RESUMEN

Studies have endeavored to understand the cause for impaired antimicrobial killing by neutrophils of people with cystic fibrosis (PWCF). The aim of this study was to focus on the bacterial phagosome. Possible alterations in degranulation of cytoplasmic granules and changes in pH were assessed. Circulating neutrophils were purified from PWCF (n = 28), PWCF receiving ivacaftor therapy (n = 10), and healthy controls (n = 28). Degranulation was assessed by Western blot analysis and flow cytometry. The pH of phagosomes was determined by use of BCECF-AM-labelled Staphylococcus aureus or SNARF labelled Candida albicans. The antibacterial effect of all treatments tested was determined by colony forming units enumeration. Bacterial killing by CF and healthy control neutrophils were found to differ (p = 0.0006). By use of flow cytometry and subcellular fractionation the kinetics of intraphagosomal degranulation were found to be significantly altered in CF phagosomes, as demonstrated by increased primary granule CD63 (p = 0.0001) and myeloperoxidase (MPO) content (p = 0.03). In contrast, decreased secondary and tertiary granule CD66b (p = 0.002) and decreased hCAP-18 and MMP-9 (p = 0.02), were observed. After 8 min phagocytosis the pH in phagosomes of neutrophils of PWCF was significantly elevated (p = 0.0001), and the percentage of viable bacteria was significantly increased compared to HC (p = 0.002). Results demonstrate that the recorded alterations in phagosomal pH generate suboptimal conditions for MPO related peroxidase, and α-defensin and azurocidine enzymatic killing of Staphylococcus aureus and Pseudomonas aeruginosa. The pattern of dysregulated MPO degranulation (p = 0.02) and prolonged phagosomal alkalinization in CF neutrophils were normalized in vivo following treatment with the ion channel potentiator ivacaftor (p = 0.04). Our results confirm that alterations of circulating neutrophils from PWCF are corrected by CFTR modulator therapy, and raise a question related to possible delayed proton channel activity in CF.


Asunto(s)
Candida albicans/inmunología , Degranulación de la Célula/inmunología , Fibrosis Quística/inmunología , Neutrófilos/inmunología , Fagosomas/inmunología , Staphylococcus aureus/inmunología , Adulto , Fibrosis Quística/microbiología , Fibrosis Quística/patología , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Neutrófilos/microbiología , Neutrófilos/patología , Fagosomas/microbiología , Fagosomas/patología
15.
Crit Care Nurse ; 37(1): 40-48, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28148613

RESUMEN

BACKGROUND: Delirium is associated with increased mortality, morbidity, hospital costs, and postdischarge cognitive dysfunction. Most research focuses on nontrauma patients receiving mechanical ventilation in the intensive care unit. OBJECTIVES: To determine the prevalence and predictors of delirium in trauma patients residing in intensive and intermediate care units of an academic medical center. METHODS: Trauma patients were screened for delirium by using the Confusion Assessment Method for the Intensive Care Unit. Exclusion criteria included documented brain injury, history of psychosis or cognitive impairment, not speaking English, and hearing or vision loss. RESULTS: Of the 215 study patients, 24% were positive for delirium; 36% of patients in the intensive care unit and 11% of patients in the intermediate care unit. Delirium-positive patients were older (mean age, 53.4 years) than patients who were not (mean age, 44 years; P = .004). Although mechanical ventilation (odds ratio, 4.73, P = .004) was the strongest independent risk factor for delirium, 12% of delirium-positive patients were not receiving mechanical ventilation. Other predictors of delirium were use of antipsychotic medications, higher scores on the Acute Physiology and Chronic Health Evaluation III, and lower scores on the Richmond Agitation-Sedation Scale. CONCLUSIONS: Patients in both the intermediate and intensive care units, whether mechanical ventilation was used or not, were positive for delirium. Delirium prevention protocols may benefit trauma patients regardless of their inpatient location.


Asunto(s)
Delirio/epidemiología , Psicotrópicos/efectos adversos , Respiración Artificial/efectos adversos , Heridas y Lesiones/complicaciones , Heridas y Lesiones/terapia , APACHE , Centros Médicos Académicos , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Delirio/etiología , Delirio/terapia , Femenino , Escala de Coma de Glasgow , Humanos , Unidades de Cuidados Intensivos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Centros Traumatológicos , Índices de Gravedad del Trauma , Población Urbana , Heridas y Lesiones/diagnóstico , Adulto Joven
16.
J Trauma Acute Care Surg ; 82(2): 387-391, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27787437

RESUMEN

BACKGROUND: No specific treatment is available for hanging-induced cardiac arrest (CA). We hypothesized that targeted temperature management (TTM) may improve the outcome of hanging-induced CA patients at hospital discharge. METHODS: A retrospective chart review of our trauma registry from January 1999 to September 2015 was conducted to identify patients 18 years or older with hanging as their injury type. All TTMs were performed to achieve 32°C to 34°C for 24 hours. The survival and Cerebral Performance Category scores at hospital discharge were determined. RESULTS: We identified 138 patients. Their average age was 32.1 ± 10.0 years; 81.3% were men, and 69.8% were white. The mortality rate was 15.2% (21 of 138). Overall, 79.7% (110 of 138) of the near-hanging patients did not sustain out-of-hospital CA (non-CA), and 1.8% of them (2 of 110) received TTM. All 110 non-CA patients survived to hospital discharge and 99.1% (109 of 110) had good neurologic outcome. The remaining 20.3% (28 of 138) of hanging patients suffered out-of-hospital CA; six of these patients were dead on arrival and thus excluded from further analysis. TTM was performed for 40.9% (9 of 22) of the remaining CA patients; 44.4% (4 of 9) of TTM CA patients survived to hospital discharge versus 23.1% (3 of 13) of non-TTM CA patients. There were no significant differences between the overall survival and patients discharged with good neurologic outcome between the TTM and non-TTM CA groups. CONCLUSION: Non-CA near-hanging patients are more likely to have favorable outcome than the CA patients. Our study was not large enough to detect survival and neurologic outcome differences between the TTM and non-TTM CA groups. A multicenter retrospective study is underway to determine the impact of TTM on the outcome of hanging-induced CA patients. LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic study, level IV.


Asunto(s)
Asfixia , Paro Cardíaco/etiología , Paro Cardíaco/terapia , Hipotermia Inducida , Intento de Suicidio , Adulto , Femenino , Paro Cardíaco/mortalidad , Humanos , Masculino , Sistema de Registros , Estudios Retrospectivos , Resultado del Tratamiento
17.
AACN Adv Crit Care ; 32(1): 27-28, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33725099
18.
J Trauma ; 62(3): 647-56; discussion 656, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17414342

RESUMEN

OBJECTIVES: Fluid therapy and/or acute lung injury may increase intra-abdominal pressure (IAP) and intrathoracic pressure, thereby increasing intracranial pressure (ICP) after traumatic brain injury (TBI). Further fluid administration to support cerebral perfusion or increasing ventilatory support to treat acute lung injury further increases ICP. This can create a cycle that ultimately produces multiple compartment syndrome (MCS). Both decompressive craniectomy (DC) and decompressive laparotomy (DL) decrease ICP. DL can also decrease IAP and ICP. We evaluated the serial application of DC and DL to treat MCS. METHODS: Data were analyzed for 102 consecutive patients with severe TBI who underwent DC alone to decrease ICP or in combination with DL to treat MCS. RESULTS: All 102 patients sustained blunt injury. Seventy percent were men with a mean age of 29.5 years, an Injury Severity Score of 34.4, and admission Glasgow Coma Scale score of 7.1. Fifty-one patients had diffuse brain injury and 51 had mass lesions. Seventy-eight patients (76%) underwent DC alone. Twenty-four (22%) had both therapies for MCS. Fifteen patients had DC before DL and nine had DL before DC. Mean time between DC and DL was 3.4 +/- 6 days. The mean IAP before DL was 28 +/- 5 mm Hg. Twenty-four-hour cumulative mean intrathoracic pressure decreased significantly after DL in the MCS group (p = 0.01). Mean ICP decreased significantly after both DC and DL (p < 0.05). CONCLUSION: Increased ICP may be from primary TBI or MCS. Patients with MCS have a higher Injury Severity Score, ICP, and fluid requirements, but no increase in mortality. Both DC and DL reduce ICP and can be used in sequence. MCS should be considered in multiply injured patients with increased ICP that does not respond to therapy.


Asunto(s)
Abdomen , Lesiones Encefálicas/complicaciones , Síndromes Compartimentales/etiología , Presión Intracraneal , Tórax , Adulto , Lesiones Encefálicas/terapia , Síndromes Compartimentales/terapia , Craneotomía , Descompresión Quirúrgica , Femenino , Fluidoterapia/efectos adversos , Escala de Coma de Glasgow , Humanos , Hipertensión Intracraneal/etiología , Hipertensión Intracraneal/terapia , Laparotomía , Masculino
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