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BACKGROUND: Advancing health equity requires more contextualised evidence. OBJECTIVES: To synthesise published evidence using an existing framework on the origins of health disparities and determine care-related outcome disparities for residents of long-term care, comparing minoritised populations to the context-specific dominant population. DESIGN: Systematic review. SUBJECTS: Residents of 24-hour long-term care homes. METHODS: The protocol was registered a priori with PROSPERO (CRD42021269489). Literature published between 1 January 2000 and 26 September 2021, was searched, including studies comparing baseline characteristics and outcomes in minoritised versus dominant populations. Dual screening, two-reviewer verification for extraction, and risk of bias assessments were conducted to ensure rigour. Studies were synthesized using a conceptual framework to contextualise evidence according to multi-level factors contributing to the development of care disparities. RESULTS: Twenty-one of 34 included studies demonstrated disparities in care outcomes for minoritised groups compared to majority groups. Thirty-one studies observed differences in individual-level characteristics (e.g. age, education, underlying conditions) upon entry to homes, with several outcome disparities (e.g. restraint use, number of medications) present at baseline and remaining or worsening over time. Significant gaps in evidence were identified, particularly an absence of literature on provider information and evidence on the experience of intersecting minority identities that contribute to care-related outcome disparities in long-term care. CONCLUSION: This review found differences in minoritised populations' care-related outcomes. The findings provide guidance for future health equity policy and research-supporting diverse and intersectional capacity building in long-term care.
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Equidad en Salud , Disparidades en Atención de Salud , Hogares para Ancianos , Cuidados a Largo Plazo , Casas de Salud , Humanos , Anciano , Masculino , FemeninoRESUMEN
OBJECTIVES: We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients. METHODS: This is a multicenter retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow-up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition. RESULTS: Of 59 pediatric patients identified at 9 centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after 1 or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; 4 (9.5%) of which were likely treatment-related. There were no deaths or infections with multidrug resistant organisms during follow-up and all patients with a SAE fully recovered. CONCLUSIONS: The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit.
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Clostridioides difficile , Infecciones por Clostridium , Adulto , Humanos , Niño , Adolescente , Trasplante de Microbiota Fecal/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Recurrencia , Infecciones por Clostridium/terapiaRESUMEN
BACKGROUND: The incidence and clinical importance of vasoplegia after lung transplantation remains poorly studied. We describe the incidence of vasoplegia and its association with complications after lung transplantation. METHODS: Perioperative data of 279 lung transplant recipients operated on from 2015 to 2020 in a UK hospital were analysed retrospectively. RESULTS: Vasoplegia occurred in 41.6% of patients after lung transplantation (mild, 31.0%; moderate, 55.2%; severe, 13.8%). Compared with non-vasoplegic patients, vasoplegic patients had a higher incidence of any acute kidney injury, defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria (78.5% vs 65%, P=0.015), renal replacement therapy (47.4% vs 24.5%, P<0.001), and delayed chest closure (18.4% vs 9.2%, P=0.025); were ventilated longer (70 [32-368] vs 34 [19-105] h, P<0.001); and stayed longer in the ICU (12.9 [5-30] vs 6.8 [3-20] days, P<0.001). Mortality at 30 days and 1 yr was higher in patients with vasoplegia (11.2% vs 5.5% and 20.7% vs 11.7%, P=0.039, respectively). Severe vasoplegia represented a predictor of longer-term mortality (hazard ratio=1.65, P=0.008). Underlying infectious disease, increased BMI, higher preoperative pulmonary artery systolic pressure and bilirubin levels, lower glomerular filtration rate, and increased fresh frozen plasma transfusion were predictors of vasoplegia severity. Neutrophilia, leucocytosis, and increased C-reactive protein were associated with vasoplegia, but release of the neutrophil activation markers myeloperoxidase and heparin-binding protein was similar between groups. CONCLUSIONS: Influenced by preoperative status as well as procedural factors and inflammatory response, vasoplegia is a common and critical condition after lung transplantation with worse short-term outcomes and long-term survival.
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Trasplante de Pulmón , Vasoplejía , Humanos , Vasoplejía/epidemiología , Vasoplejía/etiología , Estudios Retrospectivos , Incidencia , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Transfusión de Componentes Sanguíneos , Factores de Riesgo , Plasma , Trasplante de Pulmón/efectos adversosRESUMEN
Lung transplantation is the ultimate treatment for end-stage lung disease (ESLD) arising from various etiologies. This manuscript will focus on selected aspects of a theoretical perioperative lung transplantation plan, highlighting data-driven and theoretical techniques the authors would employ if they were the index patient undergoing surgery. Beginning with looking for a transplant center using an Internet search, patient advocacy organizations, and artificial intelligence guidance, the authors lay out a course for multidisciplinary care throughout the entire patient journey, ending with ideal approaches to recovery 6 months posttransplantation. Although the index case will focus on a theoretical patient with pulmonary fibrosis, the general management principles will be applicable across the entire spectrum of patients with ESLD presenting for lung transplantation.
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Enfermedades Pulmonares , Trasplante de Pulmón , Fibrosis Pulmonar , Humanos , Inteligencia Artificial , Internacionalidad , Enfermedades Pulmonares/cirugíaRESUMEN
INTRODUCTION: Preventing new parents who use drugs from bonding with and bodyfeeding their babies undermines public health. Because U.S. culture treats substance use as a moral failing rather than a health concern, punitive responses to perinatal substance use continue to dominate. This is particularly true for families of color, who are more likely to be targeted by the family regulation system. These approaches fail to protect families, and cause their own, separate harm. This article will lay out existing evidence surrounding bodyfeeding. Then, it will debunk harmful mythologies about drug use and human milk, and compare the risks associated with using drugs while bodyfeeding to those inherent in family separation. Finally, it will make the case for harm-reduction approaches over criminal ones. OBJECTIVES: The health risks associated with family separation are only rarely weighed against those associated with drug exposure through human milk. Our objective for this paper is to contribute new ways of framing the importance of keeping families together at birth, even when perinatal substance use is detected. METHODS: This manuscript is not based upon clinical study or patient data, and exclusively references studies and research publications that have been approved by the appropriate ethics committee and which have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. RESULTS: Significant research data support the position that the risks associated with family separation are arguably greater than those associated with exposure to substance use in human milk. CONCLUSIONS FOR PRACTICE: Harm reduction approaches should be favored over criminal approaches when perinatal substance use is detected or confirmed.
The harms of family separation have already been well-documented by public health and social science researchers. The risks associated with substance use and human milk have also been the subject of significant academic research. However, the authors have not come across any articles that weigh the health risks associated with family separation against those associated with drug exposure through human milk. This paper contributes new ways of framing the importance of keeping families together at birth, even when perinatal substance use is detected.
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Leche Humana , Trastornos Relacionados con Sustancias , Niño , Embarazo , Femenino , Recién Nacido , Humanos , Salud Pública , Padres , Protección a la InfanciaRESUMEN
A transformative approach to maternal health promotion should be mother-centred, context-driven and grounded in lived experiences. Health promotion can achieve this by drawing on its disciplinary roots to extend and reorient maternal health promotion towards an approach of non-stigmatizing and equitable health promotion that has mothers' well-being at the centre, particularly giving credit to marginalized, 'non-normative' maternities. This article draws on data from 18 workshops EN conducted across Aotearoa New Zealand, including 268 maternal health stakeholders. Drawing on design thinking, participants reimagined what a maternal health promotion approach informed by the Ottawa Charter action areas could comprise. The five themes included building connected systems close to home, developing mothering/parenting skills, addressing upstream determinants, mother-centred care and funding, and creating a collective mothering village. We discuss how these areas could better meet the unique challenges of transitioning to motherhood. Rather than focussing only on individual behaviours, many ideas reveal broader environmental and structural determinants. We link the themes to current literature and advance the agenda for centring the maternal in maternal health promotion.
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Promoción de la Salud , Madres , Femenino , Humanos , Nueva ZelandaRESUMEN
BACKGROUND: Antifungal stewardship (AFS) lags behind antimicrobial stewardship (AMS) in terms of implementation, evidence base, and workforce experience. Solid-organ transplantation (SOT) carries a significant risk of invasive fungal infection, with high associated mortality, and is therefore associated with significant opportunities to optimize antifungal use. METHODS: A literature search for the terms "antifungal stewardship" and "solid-organ transplant" revealed a small evidence base to support AFS programs in this patient group. RESULTS: There is significant overlap in the methodology used in AMS and AFS programs, with notable differences in diagnostics, which are discussed in detail. The primary AFS interventions tested in SOT recipients are implementation of clinical guidelines and care bundles, digital enablers of AFS, and post-prescription review/audit and feedback. CONCLUSION: There is an urgent need for further research to support effective AFS strategies in this highly susceptible population.
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Programas de Optimización del Uso de los Antimicrobianos , Infecciones Fúngicas Invasoras , Trasplante de Órganos , Antifúngicos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/métodos , Humanos , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/prevención & control , Trasplante de Órganos/efectos adversos , Trasplante de Órganos/métodos , Receptores de TrasplantesRESUMEN
BACKGROUND: The risk of complications, including death, is substantially increased in patients with pulmonary hypertension (PH) undergoing anaesthesia for surgical procedures, especially in those with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH). Sedation also poses a risk to patients with PH. Physiological changes including tachycardia, hypotension, fluid shifts, and an increase in pulmonary vascular resistance (PH crisis) can precipitate acute right ventricular decompensation and death. METHODS: A systematic literature review was performed of studies in patients with PH undergoing non-cardiac and non-obstetric surgery. The management of patients with PH requiring sedation for endoscopy was also reviewed. Using a framework of relevant clinical questions, we review the available evidence guiding operative risk, risk assessment, preoperative optimisation, and perioperative management, and identifying areas for future research. RESULTS: Reported 30 day mortality after non-cardiac and non-obstetric surgery ranges between 2% and 18% in patients with PH undergoing elective procedures, and increases to 15-50% for emergency surgery, with complications and death usually relating to acute right ventricular failure. Risk factors for mortality include procedure-specific and patient-related factors, especially markers of PH severity (e.g. pulmonary haemodynamics, poor exercise performance, and right ventricular dysfunction). Most studies highlight the importance of individualised preoperative risk assessment and optimisation and advanced perioperative planning. CONCLUSIONS: With an increasing number of patients requiring surgery in specialist and non-specialist PH centres, a systematic, evidence-based, multidisciplinary approach is required to minimise complications. Adequate risk stratification and a tailored-individualised perioperative plan is paramount.
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Consenso , Testimonio de Experto/normas , Hipertensión Pulmonar/cirugía , Atención Perioperativa/normas , Complicaciones Posoperatorias/prevención & control , Testimonio de Experto/métodos , Humanos , Hipertensión Pulmonar/diagnóstico , Atención Perioperativa/métodos , Complicaciones Posoperatorias/diagnósticoRESUMEN
Canada's healthcare sector produces the third highest healthcare-related emissions per capita globally. However, Canada has no national strategy toward environmentally sustainable healthcare. Transforming Canada's health systems to be environmentally sustainable requires leadership from many stakeholders and collaboration between trainees and health leaders. This article provides an overview of student and trainee leadership among health-related fields in response to the climate crisis and highlights the formation of a trainee-led organization focused on building capacity among emerging leaders in healthcare. We share key lessons learned by this group that are essential for all leaders seeking to leverage interdisciplinary action toward sustainable health systems in Canada.
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Programas de Gobierno , Liderazgo , Canadá , Atención a la Salud , Sector de Atención de Salud , HumanosRESUMEN
The polysaccharide-rich fungal cell wall provides pathogen-specific targets for antifungal therapy and distinct molecular patterns that stimulate protective or detrimental host immunity. The echinocandin antifungal caspofungin inhibits synthesis of cell wall ß-1,3-glucan and is used for prophylactic therapy in immune-suppressed individuals. However, breakthrough infections with fungal pathogen Aspergillus fumigatus are associated with caspofungin prophylaxis. In this study, we report in vitro and in vivo increases in fungal surface chitin in A. fumigatus induced by caspofungin that was associated with airway eosinophil recruitment in neutropenic mice with invasive pulmonary aspergillosis (IA). More importantly, caspofungin treatment of mice with IA resulted in a pattern of increased fungal burden and severity of disease that was reversed in eosinophil-deficient mice. Additionally, the eosinophil granule proteins major basic protein and eosinophil peroxidase were more frequently detected in the bronchoalveolar lavage fluid of lung transplant patients diagnosed with IA that received caspofungin therapy when compared with azole-treated patients. Eosinophil recruitment and inhibition of fungal clearance in caspofungin-treated mice with IA required RAG1 expression and γδ T cells. These results identify an eosinophil-mediated mechanism for paradoxical caspofungin activity and support the future investigation of the potential of eosinophil or fungal chitin-targeted inhibition in the treatment of IA.
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Antifúngicos/efectos adversos , Antifúngicos/farmacología , Aspergillus fumigatus/efectos de los fármacos , Quitina/metabolismo , Equinocandinas/farmacología , Eosinófilos/inmunología , Aspergilosis Pulmonar Invasiva/inmunología , Aspergilosis Pulmonar Invasiva/fisiopatología , Lipopéptidos/farmacología , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Animales , Antifúngicos/inmunología , Antifúngicos/uso terapéutico , Aspergillus fumigatus/química , Aspergillus fumigatus/inmunología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/microbiología , Caspofungina , Quitina/química , Quitina/inmunología , Equinocandinas/efectos adversos , Equinocandinas/inmunología , Equinocandinas/uso terapéutico , Eosinófilos/fisiología , Humanos , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Aspergilosis Pulmonar Invasiva/microbiología , Lipopéptidos/efectos adversos , Lipopéptidos/inmunología , Lipopéptidos/uso terapéutico , Ratones , Linfocitos T/inmunologíaRESUMEN
RATIONALE: Pulmonary aspergillosis is a lethal mold infection in the immunocompromised host. Understanding initial control of infection and how this is altered in the immunocompromised host are key goals for comprehension of the pathogenesis of pulmonary aspergillosis. OBJECTIVES: To characterize the outcome of human macrophage infection with Aspergillus fumigatus and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants. METHODS: We defined the outcome of human macrophage infection with A. fumigatus, as well as the impact of calcineurin inhibitors, through a combination of single-cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies. MEASUREMENTS AND MAIN RESULTS: Macrophage phagocytosis of A. fumigatus enabled control of 90% of fungal germination. However, fungal germination in the late phagosome led to macrophage necrosis. During programmed necroptosis, we observed frequent cell-cell transfer of A. fumigatus between macrophages, which assists subsequent control of germination in recipient macrophages. Lateral transfer occurred through actin-dependent exocytosis of the late endosome in a vasodilator-stimulated phosphoprotein envelope. Its relevance to the control of fungal germination was also shown by direct visualization in our zebrafish aspergillosis model in vivo. The calcineurin inhibitor FK506 (tacrolimus) reduced cell death and lateral transfer in vitro by 50%. This resulted in uncontrolled fungal germination in macrophages and also resulted in hyphal escape. CONCLUSIONS: These observations identify programmed, necrosis-dependent lateral transfer of A. fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host.
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Aspergillus fumigatus/metabolismo , Calcineurina/fisiología , Muerte Celular/fisiología , Macrófagos/microbiología , Aspergilosis Pulmonar/fisiopatología , Humanos , Sistema de Señalización de MAP Quinasas/fisiología , Macrófagos/patología , Macrófagos/fisiología , Necrosis , Fagocitosis/fisiología , Aspergilosis Pulmonar/inmunología , Especies Reactivas de Oxígeno/metabolismo , Esporas Fúngicas/fisiologíaRESUMEN
Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (LTx) is not uncommon, but it is not commonplace yet. We present a case of a 45-year-old man with cystic fibrosis with recent deterioration in lung function who was initially supported with veno-venous (VV) ECMO. However, he subsequently required conversion to veno-veno-arterial (VVA) ECMO. After 21 days of support, he underwent double lung transplantation, with an uneventful postoperative course. This case shows that, in patients with end-stage respiratory failure awaiting lung transplantation, extracorporeal life support may require escalation to improve gas exchange and address circulatory requirements.
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Oxigenación por Membrana Extracorpórea/métodos , Enfermedades Pulmonares/cirugía , Enfermedades Pulmonares/terapia , Trasplante de Pulmón/métodos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: As Gastroesophageal reflux disease (GORD) affects long-term survival in lung transplant recipients, the aim of this observational prospective study was to analyze the efficacy of The Reflux Symptom Index Questionnaire (RSI) compared to the esophageal impedance test. METHODS: Both esophageal impedance studies and RSI questionnaire were routinely performed in all patients who had completed rehabilitation following lung transplantation from June 2013 till March 2014. RSI generates a score of between zero and forty-five, taking into account any symptoms within four wk of the questionnaire. Our analysis considered RSI score cut-offs of 10 and 13 indicating significance of reflux. RESULTS: Out of 84 patients, 50 (59.5%) had evidence of GORD detected by impedance studies, whereas only 33 (39.2%) and 22 (26.2%) had RSI >10 and 13, respectively. An elevated RSI was not found to be associated with positive impedance studies using a score of either 10 or 13 (p = 0.127 and p = 0.142, respectively); 32.1% (n = 27) and 40.5% (n = 34) were found to have negative RSI and positive impedance test using 10 or 13 as cut-off, respectively. CONCLUSION: RSI Score is an unreliable predictor of GORD among lung transplant recipients. The authors therefore recommend the routine use of impedance testing in post-transplant patients.
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Impedancia Eléctrica , Reflujo Gastroesofágico/etiología , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón/efectos adversos , Encuestas y Cuestionarios , Femenino , Estudios de Seguimiento , Reflujo Gastroesofágico/diagnóstico , Alemania/epidemiología , Humanos , Enfermedades Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The risk-benefit for utilizing cardio-pulmonary bypass (CPB) in lung transplantation (LTx) remains debatable. This study compares outcomes after LTx utilizing different CPB strategies - elective CPB vs. off-pump vs. off-pump with unplanned conversion to CPB. METHODS: A total of 302 LTx performed over seven yr were divided into three groups: "off-pump" group (n = 86), "elective on-pump" group (n = 162), and "conversion" group (n = 54). The preoperative donor and recipient demographics and baseline characteristics and the postoperative outcomes were analyzed; 1:1 propensity score matching was used to identify patients operated upon using elective CPB who had risk profiles similar to those operated upon off-pump (propensity-matching 1) as well as those emergently converted from off-pump to CPB (propensity-matching 2). RESULTS: Preoperative group demographic characteristics were comparable; however, the "off-pump" patient group was significantly older. The "conversion" group had a significantly greater number of patients with primary pulmonary hypertension, pulmonary fibrosis, preoperative mechanical ventilation, and preoperative extracorporeal life support (ECLS). Postoperatively, patients from the "conversion" group had significantly poorer PaO2 /FiO2 ratios upon arrival in intensive care unit (ICU) and at 24, 48, and 72 h postoperatively, and they required more prolonged ventilation, longer ICU admission, and they experienced an increased need for ECLS than the other groups. Overall, cumulative survival at one, two, and three yr was significantly worse in patients from the "conversion" group compared to the "off-pump" and "elective on-pump" groups - 61.9% vs. 94.4% vs. 86.9%, 54.4% vs. 90.6% vs. 79.5% and 39.8% vs. 78.1% vs. 74.3%, respectively (p < 0.001). The "off-pump" group had significantly better PaO2 /FiO2 ratios, and a significantly shorter duration of ventilation, ICU stay, and hospital length of stay when compared to the propensity-matched "elective on-pump" group. There were no statistically significant differences in postoperative outcomes and overall survival between the "converted" group and the propensity-matched "elective on-pump" group. CONCLUSIONS: Despite segregation of unplanned CPB conversion cases from elective on-pump cases, patients with comparable preoperative demographic/risk profiles demonstrated better early postoperative outcomes and, possibly, an improved early survival with an off-pump strategy. A considerable proportion of high-risk patients require intraoperative conversion from off-pump to CPB, and this seems associated with suboptimal outcomes; however, there is no significant benefit to employing an elective on-pump strategy over emergent conversion in the high-risk group.
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Puente Cardiopulmonar , Rechazo de Injerto/diagnóstico , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón , Complicaciones Posoperatorias , Adulto , Femenino , Estudios de Seguimiento , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Periodo Posoperatorio , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: Limited data are available about lung transplantation (LTx) from donors suffering cardiac arrest (CA) prior to actual donation. METHODS: A retrospective analysis of LTx performed between January 2007 and September 2012 was done with the focus on CA in donors. The recipients were grouped depending on the history of donor CA and CA duration (downtime) as: No cardiac arrest ("NoCA"), CA downtime less than 20 min ("CA < 20"), and CA downtime equal to or more than 20 min ("CA > 20"). Early and mid-term outcomes after LTx were compared among the three groups. RESULTS: A total of 237 LTx were performed during the study period. One hundred eighty-eight patients received organs from "NoCA" donors, 25 from "CA < 20" donors, and 24 patients from "CA > 20" donors. There was a trend toward better overall cumulative survival in both CA groups (log rank p = 0.076) whereas the survival in the "CA > 20" group was significantly better than in the "NoCA" group in the subgroup analysis (log rank p = 0.045). Freedom from bronchiolitis obliterans syndrome (BOS) also increased with increase in CA duration, although it did not reach statistical significance. CONCLUSIONS: Transplantation of lungs from donors with a history of CA is safe and feasible. Longer duration of cardiac arrest may improve the outcomes after the LTx in terms of survival and freedom from BOS.
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Selección de Donante , Paro Cardíaco , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón , Complicaciones Posoperatorias , Donantes de Tejidos , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Invasive aspergillosis (IA) is a life-threatening systemic fungal infection in immunocompromised individuals that is caused by Aspergillus fumigatus. The human serum opsonin, L-ficolin, has been observed to recognize A. fumigatus and could participate in fungal defense. METHODS: Using lung epithelial cells, primary human monocyte-derived macrophages (MDMs), and neutrophils from healthy donors, we assessed phagocytosis and killing of L-ficolin-opsonized live A. fumigatus conidia by flow cytometry and microscopy. Additionally, cytokines were measured by cytometric bead array, and L-ficolin was measured in bronchoalveolar lavage (BAL) fluid from lung transplant recipients by enzyme-linked immunosorbent assay. RESULTS: L-ficolin opsonization increased conidial uptake and enhanced killing of A. fumigatus by MDMs and neutrophils. Opsonization was also shown to manifest an increase in interleukin 8 release from A549 lung epithelial cells but decreased interleukin 1ß, interleukin 6, interleukin 8, interleukin 10, and tumor necrosis factor α release from MDMs and neutrophils 24 hours after infection. The concentration of L-ficolin in BAL fluid from patients with fungal infection was significantly higher than that for control subjects (P = .00087), and receiving operating characteristic curve analysis highlighted the diagnostic potential of L-ficolin for lung infection (area under the curve, 0.842; P < .0001). CONCLUSIONS: L-ficolin modulates the immune response to A. fumigatus. Additionally, for the first time, L-ficolin has been demonstrated to be present in human lungs.
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Aspergilosis/metabolismo , Aspergillus fumigatus/inmunología , Lectinas/metabolismo , Pulmón/metabolismo , Neumonía/metabolismo , Aspergilosis/inmunología , Aspergilosis/microbiología , Línea Celular Tumoral , Citocinas/metabolismo , Humanos , Inmunidad Innata , Trasplante de Pulmón , Macrófagos/inmunología , Macrófagos/microbiología , Viabilidad Microbiana , Neutrófilos/inmunología , Neutrófilos/microbiología , Fagocitosis , Neumonía/inmunología , Neumonía/microbiología , FicolinasRESUMEN
Aspergillus fumigatus is an opportunistic fungal pathogen that typically infects the lungs of immunocompromised patients leading to a high mortality. H-Ficolin, an innate immune opsonin, is produced by type II alveolar epithelial cells and could participate in lung defences against infections. Here, we used the human type II alveolar epithelial cell line, A549, to determine the involvement of H-ficolin in fungal defence. Additionally, we investigated the presence of H-ficolin in bronchoalveolar lavage fluid from transplant patients during pneumonia. H-Ficolin exhibited demonstrable binding to A. fumigatus conidia via l-fucose, d-mannose and N-acetylglucosamine residues in a calcium- and pH-dependent manner. Moreover, recognition led to lectin complement pathway activation and enhanced fungal association with A549 cells. Following recognition, H-ficolin opsonization manifested an increase in interleukin-8 production from A549 cells, which involved activation of the intracellular signalling pathways mitogen-activated protein kinase MAPK kinase 1/2, p38 MAPK and c-Jun N-terminal kinase. Finally, H-ficolin concentrations were significantly higher in bronchoalveolar lavage fluid of patients with lung infections compared with control subjects (n = 16; P = 0·00726). Receiver operating characteristics curve analysis further highlighted the potential of H-ficolin as a diagnostic marker for lung infection (area under the curve = 0·77; P < 0·0001). Hence, H-ficolin participates in A. fumigatus defence through the activation of the lectin complement pathway, enhanced fungus-host interactions and modulated immune responses.
Asunto(s)
Células Epiteliales Alveolares/metabolismo , Aspergillus fumigatus/metabolismo , Activación de Complemento , Lectina de Unión a Manosa de la Vía del Complemento , Glicoproteínas/metabolismo , Inmunidad Innata , Lectinas/metabolismo , Pulmón/metabolismo , Neumonía/metabolismo , Aspergilosis Pulmonar/metabolismo , Células Epiteliales Alveolares/inmunología , Células Epiteliales Alveolares/microbiología , Área Bajo la Curva , Aspergillus fumigatus/inmunología , Aspergillus fumigatus/patogenicidad , Biomarcadores/metabolismo , Líquido del Lavado Bronquioalveolar/química , Estudios de Casos y Controles , Línea Celular Tumoral , Complemento C3b/inmunología , Complemento C3b/metabolismo , Glicoproteínas/inmunología , Interacciones Huésped-Patógeno , Humanos , Interleucina-8/inmunología , Interleucina-8/metabolismo , Lectinas/inmunología , Pulmón/inmunología , Pulmón/microbiología , Sistema de Señalización de MAP Quinasas , Neumonía/inmunología , Neumonía/microbiología , Valor Predictivo de las Pruebas , Aspergilosis Pulmonar/inmunología , Aspergilosis Pulmonar/microbiología , Curva ROC , Regulación hacia ArribaRESUMEN
BACKGROUND: Traditionally, patients on extracorporeal membrane oxygenation (ECMO) are sedated and mechanically ventilated, which increases risk of complications related to immobility and mechanical ventilation. The purpose of this study was to assess the feasibility and highlight the benefits of a bridge to lung transplant (LTx) using "awake ECMO" support. METHODS: The peripheral venovenous or venoarterial ECMO was implanted at a bedside. A retrospective study of patients undergoing LTx between January 2007 and March 2013 was performed. Outcomes in patients supported on ECMO as a bridge to LTx and kept "awake" (Group 1) were compared with the rest of the LTx patients (Group 2). RESULTS: In this period, 249 LTx were performed and in them 7 patients were bridged to LTx using "awake ECMO" strategy. Two patients were awake at ECMO implantation and throughout the therapy, and two patients were on ventilator support at the time of ECMO implantation who were extubated later and maintained awake until LTx. The remaining three patients were awake for some time during the ECMO. There was no statistically significant difference in most donor characteristics and recipient baseline characteristics as well as post-LTx parameters between the two groups. One-year survival estimate was not different between the groups: Group 1, 85.7% vs. Group 2, 86.3% (log rank p = 0.99). CONCLUSION: In end-stage lung disease, the ECMO can be commenced in "awake" patients and patients can be awakened on ECMO. The "awake ECMO" strategy may avoid complications related to mechanical ventilation, sedation, and immobilization and provide comparable outcomes in the high-risk LTx patients.