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Human herpes viruses (HHVs) are commonly detected in community-acquired pneumonia (CAP) patients, particularly those with complex complications, attracting increased attention from clinical practitioners. However, the significance of detecting HHVs in bronchoalveolar lavage fluid (BALF) with CAP patients is still unclear. This study retrospectively analyzed BALF samples from 64 CAP patients at the Kunming Third People's Hospital between August 2021 and December 2023. Metagenomic next generation sequencing (mNGS) was conducted on BALF samples during CAP onset. Multivariate Cox regression models were used to identify independent risk factors for 30-day all-cause mortality in CAP. HHVs were found in 84.4% of CAP patients, which were the most common pathogens (45.1%), followed by bacteria (30.2%) and fungi (11.5%). Bacterial-viral co-infections were most common, occurring in 39 patients. Notably, there was no significant difference in HHV presence between severe and non-severe CAP patients (EBV: P = 0.431, CMV: P = 0.825), except for HHV-7 (P = 0.025). In addition, there was no significant difference in the 30-day mortality between HHV positive and HHV negative groups (P = 0.470), as well as between the HHV-7 positive and HHV-7 negative groups (P = 0.910). However, neither HHVs nor HHV-7 was independent risk factors for 30-day mortality in CAP patients (HHVs: HR 1.171, P = 0.888; HHV-7: HR 1.947, P = 0.382). In summary, among the prevalent presence of multiple HHVs, EBV and CMV were the most prevalent in CAP patients. Patients with sCAP were more susceptible to HHV-7 than those with non-sCAP. These results provide valuable insights for clinicians in guiding appropriate interventions for CAP treatment.

Asunto(s)

Líquido del Lavado Bronquioalveolar , Herpesviridae , Neumonía , Humanos , Infecciones por Roseolovirus/diagnóstico , Líquido del Lavado Bronquioalveolar/virología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Neumonía/microbiología , Neumonía/mortalidad , Neumonía/terapia , Neumonía/virología , Índice de Severidad de la Enfermedad , Metagenómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Herpesviridae/genética , Herpesviridae/aislamiento & purificación

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INTRODUCTION: Severe pneumonia is a crucial issue in the development of acute kidney injury (AKI). This study evaluated the efficacy of early goal-directed renal replacement therapy (GDRRT) for the treatment of severe pneumonia-associated AKI. METHODS: In this real-world retrospective cohort study, we recruited 180 patients with severe pneumonia who were hospitalized and received GDRRT in a third-class general hospital in East China between January 1, 2017, and December 31, 2021. Clinical data on baseline characteristics, biochemical indicators, and renal replacement therapy were collected. Patients were divided into Early and Late RRT groups according to fluid status, inflammation progression, and pulmonary radiology. We investigated in-hospital all-cause mortality (primary endpoint) and renal recovery (secondary endpoint) between the two groups. RESULTS: Among the 154 recruited patients, 80 and 74 were in the early and late RRT groups, respectively. There were no significant differences in the demographic characteristics between the two groups. The duration of admission to RRT initiation was significantly shorter in Early RRT group [2.5(1.0, 8.7) d vs. 5.0(1.5,13.5) d, p = 0.027]. At RRT initiation, the patients in the Early RRT group displayed a lower percentage of fluid overload, lower doses of vasoactive agents, higher CRP levels, and higher rates of radiographic progression than those in the Late RRT group. The all-cause in-hospital mortality was significantly lower in the Early RRT group than in Late group (52.5% vs. 86.5%, p < 0.001). Patients in the Early RRT group displayed a significantly higher proportion of complete renal recovery at discharge (40.0% vs. 8.1%, p < 0.001). CONCLUSION: This study clarified that early GDRRT for the treatment of severe pneumonia-associated AKI based on fluid status and inflammation progression, was associated with reduced hospital mortality and better recovery of renal function. Our preliminary study suggests that early initiation of RRT may be an effective approach for severe pneumonia-associated AKI.

Asunto(s)

Lesión Renal Aguda , Mortalidad Hospitalaria , Neumonía , Terapia de Reemplazo Renal , Humanos , Masculino , Femenino , Lesión Renal Aguda/terapia , Lesión Renal Aguda/etiología , Lesión Renal Aguda/mortalidad , Estudios Retrospectivos , Persona de Mediana Edad , Terapia de Reemplazo Renal/métodos , Anciano , Neumonía/complicaciones , Neumonía/terapia , Neumonía/etiología , China/epidemiología , Tiempo de Tratamiento , Índice de Severidad de la Enfermedad , Resultado del Tratamiento

RESUMEN

BACKGROUND: Pneumonia stands as a significant global contributor to mortality, particularly in South Africa, where it ranks as the second leading cause of death. The country's high prevalence of HIV infection compounds this issue, significantly increasing mortality rates associated with community-acquired pneumonia (CAP). OBJECTIVE: This study aimed to audit CAP patient management at a regional rural hospital in KwaZulu-Natal. METHOD: A retrospective review of patient files from September to December 2016 was undertaken. Data extraction from clinical files, conducted according to inclusion criteria, was transferred to a data collection sheet and analyzed using SPSS version 21. RESULTS: The review encompassed 124 patient files over four months, revealing that 117 (94.4%) patients were not managed by the Standard Treatment Guidelines and Essential Medicines List for South Africa. Of the patients admitted with CAP, 54% were HIV positive, and 49 (39.5%) patients succumbed to the illness. Notably, none of the patients underwent assessment using a severity score. CONCLUSION: The findings underscore a need for more adherence to South African guidelines for managing CAP among staff at the rural regional hospital. This leads to severe consequences, exemplified by the high mortality rate. Urgent intervention is required to incorporate severity assessment scores into pneumonia evaluations, thus enabling appropriate clinical management. CONTRIBUTION: This study sheds light on the significant impact of CAP within the South African hospital context, delineating critical gaps in clinical care and emphasizing the imperative to address clinical inertia.

Asunto(s)

Infecciones Comunitarias Adquiridas , Infecciones por VIH , Hospitales Rurales , Neumonía , Humanos , Sudáfrica/epidemiología , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/mortalidad , Infecciones Comunitarias Adquiridas/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Adulto , Neumonía/mortalidad , Neumonía/tratamiento farmacológico , Neumonía/epidemiología , Neumonía/terapia , Persona de Mediana Edad , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/mortalidad , Infecciones por VIH/epidemiología , Adulto Joven , Anciano , Adhesión a Directriz , Antibacterianos/uso terapéutico

RESUMEN

BACKGROUND: Evidence-based practice in community-acquired pneumonia often assumes an accurate initial diagnosis. OBJECTIVE: To examine the evolution of pneumonia diagnoses among patients hospitalized from the emergency department (ED). DESIGN: Retrospective nationwide cohort. SETTING: 118 U.S. Veterans Affairs medical centers. PATIENTS: Aged 18 years or older and hospitalized from the ED between 1 January 2015 and 31 January 2022. MEASUREMENTS: Discordances between initial pneumonia diagnosis, discharge diagnosis, and radiographic diagnosis identified by natural language processing of clinician text, diagnostic coding, and antimicrobial treatment. Expressions of uncertainty in clinical notes, patient illness severity, treatments, and outcomes were compared. RESULTS: Among 2 383 899 hospitalizations, 13.3% received an initial or discharge diagnosis and treatment of pneumonia: 9.1% received an initial diagnosis and 10.0% received a discharge diagnosis. Discordances between initial and discharge occurred in 57%. Among patients discharged with a pneumonia diagnosis and positive initial chest image, 33% lacked an initial diagnosis. Among patients diagnosed initially, 36% lacked a discharge diagnosis and 21% lacked positive initial chest imaging. Uncertainty was frequently expressed in clinical notes (58% in ED; 48% at discharge); 27% received diuretics, 36% received corticosteroids, and 10% received antibiotics, corticosteroids, and diuretics within 24 hours. Patients with discordant diagnoses had greater uncertainty and received more additional treatments, but only patients lacking an initial pneumonia diagnosis had higher 30-day mortality than concordant patients (14.4% [95% CI, 14.1% to 14.7%] vs. 10.6% [CI, 10.4% to 10.7%]). Patients with diagnostic discordance were more likely to present to high-complexity facilities with high ED patient load and inpatient census. LIMITATION: Retrospective analysis; did not examine causal relationships. CONCLUSION: More than half of all patients hospitalized and treated for pneumonia had discordant diagnoses from initial presentation to discharge. Treatments for other diagnoses and expressions of uncertainty were common. These findings highlight the need to recognize diagnostic uncertainty and treatment ambiguity in research and practice of pneumonia-related care. PRIMARY FUNDING SOURCE: The Gordon and Betty Moore Foundation.

Asunto(s)

Infecciones Comunitarias Adquiridas , Hospitales de Veteranos , Neumonía , Humanos , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/terapia , Estudios Retrospectivos , Estados Unidos/epidemiología , Incertidumbre , Neumonía/diagnóstico , Neumonía/tratamiento farmacológico , Neumonía/terapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , Servicio de Urgencia en Hospital/estadística & datos numéricos , Antibacterianos/uso terapéutico , Hospitalización , Errores Diagnósticos , Adulto , Alta del Paciente

RESUMEN

The reportedly poor outcome of late-onset idiopathic pneumonia syndrome (IPS) necessitates new approaches to its treatment. A 55-year-old man who had undergone allogeneic hematopoietic cell transplantation (allo-HCT) for myelodysplastic syndrome 1 year ago developed dyspnea with acute skin graft-versus-host disease (GVHD) flare-up while tapering immunosuppressive agents. He presented with acute respiratory distress syndrome with ground-glass opacities in the right upper and left lower lobes. All infectious tests, including multiplex polymerase chain reaction of nasal wash, were negative, and broad-spectrum antibiotic therapy was refractory. The patient was diagnosed with late-onset IPS and was refractory to methylprednisolone pulse therapy. He then showed a favorable response to mesenchymal stem cell (MSC) infusion. After eight infusions of MSCs, he had no IPS recurrence for over one year. Recently, preclinical studies have reported the potential therapeutic utility of MSC infusion for treating IPS, and our case supports its potential for treating late-onset IPS.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre Mesenquimatosas , Trasplante Homólogo , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/terapia , Enfermedad Injerto contra Huésped , Células Madre Mesenquimatosas , Metilprednisolona/uso terapéutico , Neumonía/etiología , Neumonía/terapia , Síndrome

RESUMEN

BACKGROUND: Most of the current bacteriophages (phages) are mostly isolated from environments. However, phages isolated from feces might be more specific to the bacteria that are harmful to the host. Meanwhile, some phages from the environment might affect non-pathogenic bacteria for the host. METHODS: Here, bacteriophages isolated from mouse feces were intratracheally (IT) or intravenously (IV) administered in pneumonia mice caused by Pseudomonas aeruginosa at 2 hours post-intratracheal bacterial administration. As such, the mice with phage treatment, using either IT or IV administration, demonstrated less severe pneumonia as indicated by mortality, serum cytokines, bacteremia, bacterial abundance in bronchoalveolar lavage fluid (BALF), and neutrophil extracellular traps (NETs) in lung tissue (immunofluorescence of neutrophil elastase and myeloperoxidase). RESULTS: Interestingly, the abundance of phages in BALF from the IT and IV injections was similar, supporting a flexible route of phage administration. With the incubation of bacteria with neutrophils, the presence of bacteriophages significantly improved bactericidal activity, but not NETs formation, with the elevated supernatant IL-6 and TNF-α, but not IL-1ß. In conclusion, our findings suggest that bacteriophages against Pseudomonas aeruginosa can be discovered from feces of the host. CONCLUSIONS: The phages attenuate pneumonia partly through an enhanced neutrophil bactericidal activity, but not via inducing NETs formation. The isolation of phages from the infected hosts themselves might be practically useful for future treatment. More studies are warranted.

Asunto(s)

Heces , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Animales , Pseudomonas aeruginosa/virología , Heces/microbiología , Heces/virología , Ratones , Infecciones por Pseudomonas/terapia , Infecciones por Pseudomonas/microbiología , Líquido del Lavado Bronquioalveolar/microbiología , Líquido del Lavado Bronquioalveolar/virología , Neutrófilos/inmunología , Bacteriófagos/aislamiento & purificación , Bacteriófagos/fisiología , Trampas Extracelulares , Neumonía/microbiología , Neumonía/terapia , Neumonía/virología , Citocinas/metabolismo , Citocinas/sangre , Terapia de Fagos/métodos , Femenino , Pulmón/microbiología , Pulmón/virología , Neumonía Bacteriana/terapia , Neumonía Bacteriana/microbiología

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This review article explores the respiratory aspects of primary ciliary dyskinesia (PCD), a rare, heterogenous, genetic disorder characterized by impaired motile ciliary function. It discusses the clinical diagnosis and management strategies for PCD-related respiratory disease, including chronic sinusitis, otitis media with effusion, recurrent pneumonia, and bronchiectasis. The review emphasizes the need for a multidisciplinary approach to optimize care and clinical trials to improve outcomes in individuals with PCD, highlighting the importance of accurate diagnosis.

Asunto(s)

Bronquiectasia , Síndrome de Kartagener , Humanos , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/terapia , Síndrome de Kartagener/fisiopatología , Síndrome de Kartagener/complicaciones , Bronquiectasia/terapia , Bronquiectasia/fisiopatología , Bronquiectasia/diagnóstico , Sinusitis/terapia , Sinusitis/diagnóstico , Sinusitis/fisiopatología , Otitis Media con Derrame/diagnóstico , Otitis Media con Derrame/fisiopatología , Otitis Media con Derrame/terapia , Neumonía/diagnóstico , Neumonía/terapia , Neumonía/fisiopatología

RESUMEN

Despite significant efforts toward improving therapy for septic shock, mortality remains high. Applying veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) in this context remains controversial. Since the cannulation of the femoral artery for V-A ECMO return leads to lower body hyperoxia, this study investigated the impact of V-A ECMO therapy on the intestinal and hepatic microcirculation during septic shock in a rodent model. Thirty male Lewis rats were randomly assigned to receive V-A ECMO therapy with low (60 mL/kg/min) or high (90 mL/kg/min) blood flow or a sham procedure. Hemodynamic data were collected through a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by intravenous administration of lipopolysaccharide (1 mg/kg). The rats received lung-protective ventilation during V-A ECMO therapy. The hepatic and intestinal microcirculation was measured by micro-lightguide spectrophotometry after median laparotomy for two hours. Systemic and pulmonary inflammation was detected via enzyme-linked immunosorbent assays (ELISA) of the plasma and bronchoalveolar lavage (BAL), respectively, measuring tumor necrosis factor-alpha (TNF-α), interleukins 6 (IL-6) and 10 (IL-10), and C-X-C motif ligands 2 (CXCL2) and 5 (CXCL5). Oxygen saturation and relative hemoglobin concentration were reduced in the hepatic and intestinal microcirculation during V-A ECMO therapy, independent of the blood flow rate. Further, rats treated with V-A ECMO therapy also presented elevated systolic, diastolic, and mean arterial blood pressure and increased stroke volume, cardiac output, and left ventricular end-diastolic volume. However, left ventricular end-diastolic pressure was only elevated during high-flow V-A ECMO therapy. Blood gas analysis revealed a dilutional anemia during V-A ECMO therapy. ELISA analysis showed an elevated plasma CXCL2 concentration only during high-flow V-A ECMO therapy and elevated BAL CXCL2 and CXCL5 concentrations only during low-flow V-A ECMO therapy. Rats undergoing V-A ECMO therapy exhibited impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Increased pulmonary inflammation was detected only during low-flow V-A ECMO therapy in septic shock.

Asunto(s)

Modelos Animales de Enfermedad , Oxigenación por Membrana Extracorpórea , Intestinos , Hígado , Microcirculación , Ratas Endogámicas Lew , Choque Séptico , Animales , Oxigenación por Membrana Extracorpórea/métodos , Masculino , Ratas , Choque Séptico/terapia , Choque Séptico/fisiopatología , Choque Séptico/metabolismo , Hígado/metabolismo , Hígado/irrigación sanguínea , Intestinos/irrigación sanguínea , Neumonía/terapia , Neumonía/metabolismo , Neumonía/fisiopatología , Hemodinámica , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangre

RESUMEN

BACKGROUND: Pulmonary fibrosis is a progressive disease with high incidence and poor prognosis. It is urgent to explore new therapeutic methods for pulmonary fibrosis. As a new treatment method, gene therapy has attracted more and more attention. CCDC59 is a transcriptional coactivator of SP-B and SP-C. Our study mainly aims to explore the effect of overexpression of CCDC59 gene in pulmonary fibrosis of mice. METHODS: CCDC59 overexpressing lentivirus was constructed and then concentrated. RT-qPCR, Western blotting, and immunofluorescence assays were used to detect the expression of CCDC59, SP-B and SP-C protein in cell line and lung tissues after infected with lentivirus. Immunohistochemical staining and hematoxylin-eosin staining assays were used to assess the degree of fibrosis and ELISA assay was used to detect the concentrations of inflammatory factors, SP-B, and SP-C in bronchoalveolar lavage fluid of mice. Dynamic changes of mice lung function at various time points were assessed by lung function test assay. HIPPO pathway and proliferation capacity of alveolar type II epithelial cells were evaluated by immunofluorescence staining and Western blotting. RESULTS: Results showed that endotracheal instillation of CCDC59 overexpressed lentivirus significantly alleviated bleomycin-induced inflammation and pulmonary fibrosis in mice. Overexpression of CCDC59 protein in type II alveolar epithelial cells can enhance the expression of SP-B and SP-C. Overexpression of CCDC59 protein significantly protected against pulmonary inflammatory response and improved lung function of mice. Overexpression of CCDC59 protein significantly alleviated the hyperactivation of HIPPO pathway and increased the proliferative capacity of type II alveolar epithelial cells in lung. CONCLUSION: CCDC59 can alleviate inflammation and pulmonary fibrosis in mice by upregulating the expression of SP-B and SP-C in type II alveolar epithelial cells and alleviating the hyperactivation of HIPPO pathway. Our study offers a new potential treatment for pulmonary fibrosis.

Asunto(s)

Fibrosis Pulmonar , Proteína C Asociada a Surfactante Pulmonar , Animales , Humanos , Masculino , Ratones , Bleomicina , Modelos Animales de Enfermedad , Lentivirus/genética , Pulmón/patología , Pulmón/metabolismo , Ratones Endogámicos C57BL , Neumonía/inducido químicamente , Neumonía/genética , Neumonía/terapia , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/terapia , Proteína C Asociada a Surfactante Pulmonar/genética , Proteína C Asociada a Surfactante Pulmonar/metabolismo

RESUMEN

Acute respiratory distress syndrome (ARDS) is a severe lung disease of high mortality (30-50%). Patients require lifesaving supplemental oxygen therapy; however, hyperoxia can induce pulmonary inflammation and cellular damage. Although alveolar macrophages (AMs) are essential for lung immune homeostasis, they become compromised during inflammatory lung injury. To combat this, stem cell-derived alveolar-like macrophages (ALMs) are a prospective therapeutic for lung diseases like ARDS. Using in vitro and in vivo approaches, we investigated the impact of hyperoxia on murine ALMs during acute inflammation. In vitro, ALMs retained their viability, growth, and antimicrobial abilities when cultured at 60% O2, whereas they die at 90% O2. In contrast, ALMs instilled in mouse lungs remained viable during exposure of mice to 90% O2. The ability of the delivered ALMs to phagocytose Pseudomonas aeruginosa was not impaired by exposure to 60 or 90% O2. Furthermore, ALMs remained immunologically stable in a murine model of LPS-induced lung inflammation when exposed to 60 and 90% O2 and effectively attenuated the accumulation of CD11b+ inflammatory cells in the airways. These results support the potential use of ALMs in patients with ARDS receiving supplemental oxygen therapy.NEW & NOTEWORTHY The current findings support the prospective use of stem cell-derived alveolar-like macrophages (ALMs) as a therapeutic for inflammatory lung disease such as acute respiratory distress syndrome (ARDS) during supplemental oxygen therapy where lungs are exposed to high levels of oxygen. Alveolar-like macrophages directly delivered to mouse lungs were found to remain viable, immunologically stable, phagocytic toward live Pseudomonas aeruginosa, and effective in reducing CD11b+ inflammatory cell numbers in LPS-challenged lungs during moderate and extreme hyperoxic exposure.

Asunto(s)

Modelos Animales de Enfermedad , Hiperoxia , Lipopolisacáridos , Macrófagos Alveolares , Neumonía , Pseudomonas aeruginosa , Animales , Hiperoxia/complicaciones , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/patología , Macrófagos Alveolares/metabolismo , Ratones , Neumonía/patología , Neumonía/inducido químicamente , Neumonía/inmunología , Neumonía/terapia , Ratones Endogámicos C57BL , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/inmunología , Síndrome de Dificultad Respiratoria/patología , Síndrome de Dificultad Respiratoria/inducido químicamente , Fagocitosis , Masculino , Pulmón/patología , Pulmón/inmunología

RESUMEN

Treatment of critically ill patients with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance in the last few decades. However, the use of V-V ECMO in septic shock remains controversial. The effect of ECMO-induced inflammation on the microcirculation of the intestine, liver, and critically damaged lungs is unknown. Therefore, the aim of this study was to measure the hepatic and intestinal microcirculation and pulmonary inflammatory response in a model of V-V ECMO and septic shock in the rat. Twenty male Lewis rats were randomly assigned to receive V-V ECMO therapy or a sham procedure. Hemodynamic data were measured by a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by the intravenous infusion of lipopolysaccharide (1 mg/kg). During V-V ECMO therapy, rats received lung-protective ventilation. The hepatic and intestinal microcirculation was assessed by micro-lightguide spectrophotometry after median laparotomy for 2 h. Systemic and pulmonary inflammation was measured by enzyme-linked immunosorbent assays of plasma and bronchoalveolar lavage (BAL), respectively, which included tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-10, C-X-C motif ligand 2 (CXCL2), and CXCL5. Reduced oxygen saturation and relative hemoglobin concentration were measured in the hepatic and intestinal microcirculation during treatment with V-V ECMO. These animals also showed increased systolic, mean, and diastolic blood pressures. While no differences in left ventricular ejection fraction were observed, animals in the V-V ECMO group presented an increased heart rate, stroke volume, and cardiac output. Blood gas analysis showed dilutional anemia during V-V ECMO, whereas plasma analysis revealed a decreased concentration of IL-10 during V-V ECMO therapy, and BAL measurements showed increased concentrations of TNF-α, CXCL2, and CXCL5. Rats treated with V-V ECMO showed impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Despite lung-protective ventilation, increased pulmonary inflammation was recognized during V-V ECMO therapy in septic shock.

Asunto(s)

Modelos Animales de Enfermedad , Oxigenación por Membrana Extracorpórea , Intestinos , Hígado , Microcirculación , Ratas Endogámicas Lew , Choque Séptico , Animales , Oxigenación por Membrana Extracorpórea/métodos , Masculino , Ratas , Choque Séptico/terapia , Choque Séptico/fisiopatología , Choque Séptico/metabolismo , Intestinos/irrigación sanguínea , Hígado/metabolismo , Hígado/irrigación sanguínea , Neumonía/terapia , Neumonía/metabolismo , Neumonía/fisiopatología , Hemodinámica , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangre

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INTRODUCTION: Childhood pneumonia is a leading cause of morbidity and mortality among children aged 2-59 months, particularly in low-income and middle-income countries (LMICs), where healthcare providers face significant challenges in diagnosing and treating childhood pneumonia. Many LMICs have taken steps to address this issue by revising their national policies and aligning them with WHO's revised guidelines for pneumonia management. These revised guidelines aim to facilitate the outpatient management of children aged 2-59 months chest indrawing pneumonia. Despite these efforts, there is limited empirical evidence regarding the management and outcomes of these children in primary-level healthcare settings. This study aims to assess the survival status of children aged 2-59 months with chest indrawing pneumonia presenting at primary healthcare facilities. METHODS AND ANALYSIS: A prospective, observational cohort study will be conducted in Ethiopia, Nigeria, Uganda, Zambia, India and Pakistan on children aged 2-59 months presenting at selected primary-level healthcare facilities with chest indrawing pneumonia. Eligible participants will be enrolled and managed by facility healthcare providers who are trained in Integrated Management of Childhood Illness and will be followed up on day 15 to record the treatment-related information and vital status, including conducting verbal autopsies in case of child death. The sample size for each site will be 310. The analysis will involve exploring site-specific trends before conducting a pooled analysis of de-identified data from all sites. The first data collection started at the Ethiopian site in September 2022, followed by other sites. The data collection will continue until June 2025. ETHICS AND DISSEMINATION: The study protocol, enrolment forms and consent forms will undergo ethical review by the Institutional Review Boards of the University of Gondar, Gondar, Ethiopia; the INCLEN Trust International Independent Ethics Committee, New Delhi, India; Ethical Review Committee of the University of Ibadan, Ethical Review Committees of Lagos State and Ethical Review Committee of University College London, UK; Institutional Review Board, International Research Force, Islamabad, Pakistan; Institutional Review Board, People's Primary Healthcare Initiative-Sindh, Karachi and National Bioethics Committee, Islamabad, Pakistan; Makerere University School of Biomedical Sciences Research Ethical Committee, Kampala, Uganda; University of Zambia Biomedical Research Ethics committee, Lusaka, Zambia and Ethical Review Committee of WHO, Geneva, Switzerland. Ethical procedures include WHO and local review board evaluations, parental consent in the local/national language, permits enrolment, follow-up, and, if required, clinical video recording for children with chest indrawing pneumonia, ensuring their eligibility. Adherence to local regulations encompasses precollection ethical approvals, risk management strategies and secure, de-identified data storage. Findings will be disseminated through seminars, publications and meetings, engaging diverse stakeholders to foster collaborations. TRIAL REGISTRATION NUMBER: ISRCTN12687253.

Asunto(s)

Neumonía , Humanos , Lactante , Neumonía/terapia , Preescolar , Estudios Prospectivos , Uganda/epidemiología , Pakistán/epidemiología , India/epidemiología , Femenino , Estudios Observacionales como Asunto , Masculino , Zambia/epidemiología , Nigeria , Etiopía/epidemiología

RESUMEN

Acinetobacter baumannii, an opportunistic pathogen, poses a significant threat in intensive care units, leading to severe nosocomial infections. The rise of multi-drug-resistant strains, particularly carbapenem-resistant A. baumannii, has created formidable challenges for effective treatment. Given the prolonged development cycle and high costs associated with antibiotics, phages have garnered clinical attention as an alternative for combating infections caused by drug-resistant bacteria. However, the utilization of phage therapy encounters notable challenges, including the narrow host spectrum, where each phage targets a limited subset of bacteria, increasing the risk of phage resistance development. Additionally, uncertainties in immune system dynamics during treatment hinder tailoring symptomatic interventions based on patient-specific states. In this study, we isolated two A. baumannii phages from wastewater and conducted a comprehensive assessment of their potential applications. This evaluation included sequencing analysis, genome classification, pH and temperature stability assessments, and in vitro bacterial inhibition assays. Further investigations involved analyzing histological and cytokine alterations in rats undergoing phage cocktail treatment for pneumonia. The therapeutic efficacy of the phages was validated, and transcriptomic studies of rat lung tissue during phage treatment revealed crucial changes in the immune system. The findings from our study underscore the potential of phages for future development as a treatment strategy and offer compelling evidence regarding immune system dynamics throughout the treatment process.IMPORTANCEDue to the growing problem of multi-drug-resistant bacteria, the use of phages is being considered as an alternative to antibiotics, and the genetic safety and application stability of phages determine the potential of phage application. The absence of drug resistance genes and virulence genes in the phage genome can ensure the safety of phage application, and the fact that phage can remain active in a wide range of temperatures and pH is also necessary for application. In addition, the effect evaluation of preclinical studies is especially important for clinical application. By simulating the immune response situation during the treatment process through mammalian models, the changes in animal immunity can be observed, and the effect of phage therapy can be further evaluated. Our study provides compelling evidence that phages hold promise for further development as therapeutic agents for Acinetobacter baumannii infections.

Asunto(s)

Infecciones por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Carbapenémicos , Modelos Animales de Enfermedad , Terapia de Fagos , Acinetobacter baumannii/virología , Acinetobacter baumannii/efectos de los fármacos , Animales , Infecciones por Acinetobacter/terapia , Infecciones por Acinetobacter/microbiología , Ratas , Terapia de Fagos/métodos , Carbapenémicos/farmacología , Bacteriófagos/fisiología , Bacteriófagos/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Masculino , Genoma Viral , Aguas Residuales , Neumonía/terapia , Neumonía/microbiología , Neumonía/virología

RESUMEN

Objective: Metagenomic sequencing (mNGS) is a promising technique for pathogen detection. However, the use of mNGS in pediatric lung infections is still rarely reported. Methods: A total of 59 cases were included between January 2019 and December 2021. To compare the performance of mNGS and routine detection in diagnosing pulmonary infection and identifying pathogenic bacteria. Results: 59 children (33.90%) were infected with Mycoplasma pneumoniae, 15 were infected with adenovirus type 7 (25.42%), 11 were infected with Streptococcus pneumoniae (18.64%), 6 were infected with Staphylococcus aureus (10.17%), 5 were infected with Klebsiella pneumoniae, Acinetobacter baumannii, pertussis, and oral streptococcus (8.47%), 3 were infected with Haemophilus influenzae (5.08%), and 3 were infected with Pseudomonas aeruginosa (5.08%). Among 59 patients, 41 were co-infected with multiple pathogens and 18 were infected with independent pathogens. Mycoplasma pneumoniae infection was most common in 6 out of 18 independent pathogen patients (33%). Among them were 3 cases of type 7 adenovirus, 53 cases of human herpesvirus (16.7%), and 2 cases of pertussis bacillus (11.1%). One case (5.6%) was infected with Streptococcus pneumoniae, Proteus albicans, Mycobacterium tuberculosis, Staphylococcus aureus, and Klebsiella pneumoniae. In cases where routine testing results are negative, mNGS improves the diagnostic efficiency of mixed pulmonary infections. 17 cases (17/59=28.81%) were diagnosed as single infection through routine testing, and the mNGS results of 4 cases were consistent with routine testing, all of which were Mycoplasma pneumoniae infections. Three cases were tested for partial mNGS matching, of which one case tested positive for Mycoplasma pneumoniae antibody and tested positive for Mycoplasma pneumoniae infection and human infection γ Herpes virus type 4, one case tested positive for antibodies and tested for infection with Mycoplasma pneumoniae and Streptococcus pneumoniae. The routine examination results of the remaining 11 patients were inconsistent with the mNGS examination results. Two patients tested positive for Mycoplasma antibodies. Patient 17 presented with mNGS infection of Haemophilus, Neisseria, and adenovirus type 7, while another patient 18 presented with herpes virus type 5 infection. Conclusion: mNGS is a promising technique for detecting co-pathogens in mixed pediatric lung infections, with potential benefits in terms of speed and sensitivity.

Asunto(s)

Líquido del Lavado Bronquioalveolar , Humanos , Masculino , Femenino , Preescolar , Niño , Líquido del Lavado Bronquioalveolar/microbiología , Líquido del Lavado Bronquioalveolar/virología , Metagenómica/métodos , Lactante , Adolescente , Neumonía/diagnóstico , Neumonía/microbiología , Neumonía/terapia

Asunto(s)

Neumonía , Toxoplasma , Toxoplasmosis , Zoonosis , Femenino , Humanos , Broncoscopía , Ácidos Nucleicos Libres de Células/sangre , Infecciones Comunitarias Adquiridas/sangre , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/etiología , Infecciones Comunitarias Adquiridas/terapia , ADN Protozoario/sangre , ADN Protozoario/aislamiento & purificación , Hipoxia/sangre , Hipoxia/diagnóstico , Hipoxia/etiología , Hipoxia/terapia , Inmunocompetencia , Anamnesis , Neumonía/sangre , Neumonía/diagnóstico , Neumonía/etiología , Neumonía/terapia , Insuficiencia Respiratoria/sangre , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/terapia , Toxoplasma/aislamiento & purificación , Toxoplasmosis/sangre , Toxoplasmosis/diagnóstico , Toxoplasmosis/etiología , Toxoplasmosis/terapia , Resultado del Tratamiento , Zoonosis/sangre , Zoonosis/diagnóstico , Zoonosis/etiología , Zoonosis/terapia , Ciervos/parasitología

RESUMEN

BACKGROUND: In Uganda, village health workers (VHWs) manage childhood illness under the integrated community case management (iCCM) strategy. Care is provided for malaria, pneumonia, and diarrhoea in a community setting. Currently, there is limited evidence on the cost-effectiveness of iCCM in comparison to health facility-based management for childhood illnesses. This study examined the cost-effectiveness of the management of childhood illness using the VHW-led iCCM against health facility-based services in rural south-western Uganda. METHODS: Data on the costs and effectiveness of VHW-led iCCM versus health facility-based services for the management of childhood illness was collected in one sub-county in rural southwestern Uganda. Costing was performed using the ingredients approach. Effectiveness was measured as the number of under-five children appropriately treated. The Incremental Cost-Effectiveness Ratio (ICER) was calculated from the provider perspective. RESULTS: Based on the decision model for this study, the cost for 100 children treated was US$628.27 under the VHW led iCCM and US$87.19 for the health facility based services, while the effectiveness was 77 and 71 children treated for VHW led iCCM and health facility-based services, respectively. An ICER of US$6.67 per under five-year child treated appropriately for malaria, pneumonia and diarrhoea was derived for the provider perspective. CONCLUSION: The health facility based services are less costly when compared to the VHW led iCCM per child treated appropriately. The VHW led iCCM was however more effective with regard to the number of children treated appropriately for malaria, pneumonia and diarrhoea. Considering the public health expenditure per capita for Uganda as the willingness to pay threshold, VHW led iCCM is a cost-effective strategy. VHW led iCCM should, therefore, be enhanced and sustained as an option to complement the health facility-based services for treatment of childhood illness in rural contexts.

Asunto(s)

Manejo de Caso , Agentes Comunitarios de Salud , Análisis Costo-Beneficio , Población Rural , Uganda , Humanos , Agentes Comunitarios de Salud/economía , Manejo de Caso/economía , Preescolar , Lactante , Malaria/economía , Malaria/tratamiento farmacológico , Diarrea/terapia , Diarrea/economía , Neumonía/economía , Neumonía/terapia , Instituciones de Salud/economía , Instituciones de Salud/estadística & datos numéricos , Recién Nacido , Masculino , Femenino , Servicios de Salud Comunitaria/economía

RESUMEN

OBJECTIVE: To investigate the effect of prone position on the prognosis of patients with severe pneumonia in intensive care unit (ICU). METHODS: A retrospective cohort study was conducted. The patients with severe pneumonia admitted to the ICU of Qingdao Municipal Hospital from May 2022 to August 2023 were enrolled. The general information, etiology, underlying diseases, vital signs and laboratory indicators at ICU admission, clinical treatment and prognosis during ICU hospitalization were collected. The above clinical data of patients with different prognosis were compared. Multifactorial Logistic regression analysis was used to screen the related factors affecting survival during ICU in patients with severe pneumonia. The change in oxygenation index (PaO2/FiO2) of patients with severe pneumonia were observed at 1 hour before the first prone position, 1 hour after the first prone position, and 1 hour after the end of the first prone position. The effect of prone position on oxygenation in patients with severe pneumonia was analyzed. Spearman correlation analysis was used to investigate the correlation between the duration to first prone position and the change in the PaO2/FiO2 before and after prone position in patients with severe pneumonia. RESULTS: Finally, a total of 144 patients with severe pneumonia were enrolled, 45 survived and 99 died during ICU hospitalization, with a mortality of 68.8%. Compared with the survival group, the patients in the death group were older [years old: 81.00 (70.75, 86.00) vs. 71.00 (60.50, 81.50), P < 0.01], the proportion of pre-existing lung disease, heart rate (HR), respiratory rate (RR), blood lactic acid (Lac) and the ratio of continuous renal replacement therapy (CRRT) were higher [ratio of pre-existing lung disease: 23.2% (23/99) vs. 8.9% (4/45), HR (bpm): 99.61±22.47 vs. 91.49±18.76, RR (times/min): 22.50 (19.75, 29.25) vs. 20.00 (17.50, 24.50), Lac (mmol/L): 2.00 (1.55 , 3.25) vs. 1.60 (1.20, 1.95), CRRT ratio: 25.3% (25/99) vs. 6.7% (3/45), all P < 0.05], and the proportion of prone position was lower [41.4% (41/99) vs. 68.9% (31/45), P < 0.01]. Multifactorial Logistic regression analysis showed that age [odds ratio (OR) = 0.946, 95% confidence interval (95%CI) was 0.912-0.980, P = 0.002] and Lac (OR = 0.563, 95%CI was 0.340-0.930, P = 0.025) were negatively correlated with survival during ICU hospitalization in severe pneumonia patients, while prone position was positively correlated with survival (OR = 2.551, 95%CI was 1.067-6.095, P = 0.035), indicating that prone position was beneficial for improving ICU prognosis in severe pneumonia patients. The results of PaO2/FiO2 at different time points in prone position showed that PaO2/FiO2 at 1 hour of the first prone position in the patients with severe pneumonia was significantly higher than that at 1 hour before the first prone position [mmHg (1 mmHg ≈ 0.133 kPa): 146.69 (113.92, 257.25) vs. 111.75 (70.15, 212.20), P < 0.01], indicating that the prone position had a relevant effect on the improvement of oxygenation in patients. Spearman correlation analysis showed that the duration of the first prone position in patients with severe pneumonia was significantly and positively correlated with the improvement of oxygenation at 1 hour of the first prone position (r = 0.565, P < 0.001). CONCLUSIONS: The prone position is a therapeutic measure that can independently influence the prognosis of patients with severe pneumonia during ICU hospitalization. The prone position effectively improves oxygenation in patients with severe pneumonia and the first change in oxygenation in patients is related to the duration of the prone position.

Asunto(s)

Unidades de Cuidados Intensivos , Neumonía , Humanos , Posición Prona , Estudios Retrospectivos , Neumonía/terapia , Pronóstico , Masculino , Femenino

RESUMEN

OBJECTIVE: To describe the successful conservative management of chemical pneumonitis and presumed acute respiratory distress syndrome in a cat secondary to inadvertent pulmonary polyethylene glycol-electrolyte solution (PEG-ELS) instillation. CASE SUMMARY: PEG-ELS is commonly used in small animals for bowel cleansing and to treat constipation. There have been several instances of aspiration or accidental instillation of this solution into the lungs of both people and dogs. PEG-ELS was inadvertently infused into the lungs of the cat in the current report. After 10 days in the ICU, during which time treatment with oxygen therapy, antibiosis, diuretics, and corticosteroids was provided, the cat was successfully discharged. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first report of instillation of PEG-ELS in a cat resulting in chemical pneumonitis and lung injury. We describe the successful management of this condition with conservative management and without the need for invasive interventions such as bronchoscopy and lavage or mechanical ventilation.

Asunto(s)

Enfermedades de los Gatos , Polietilenglicoles , Gatos , Animales , Polietilenglicoles/efectos adversos , Polietilenglicoles/administración & dosificación , Enfermedades de los Gatos/inducido químicamente , Enfermedades de los Gatos/terapia , Electrólitos/administración & dosificación , Electrólitos/uso terapéutico , Neumonía/veterinaria , Neumonía/inducido químicamente , Neumonía/terapia , Masculino , Femenino

RESUMEN

OBJECTIVES: To determine the impact of telementoring on caregiver performance during a high-fidelity medical simulation model (HFMSM) of a critically ill patient in a resource-limited setting. DESIGN: A two-center, randomized, controlled study using a HFMSM of a patient with community-acquired pneumonia complicated by acute respiratory distress syndrome. SETTING: A notional clinic in a remote location staffed by a single clinician and nonmedical assistant. PARTICIPANTS: Clinicians with limited experience managing critically ill patients. INTERVENTIONS: Telemedicine (TM) support. MEASUREMENTS: The primary outcome was clinical performance as measured by accuracy, reliability, and efficiency of care. Secondary outcomes were patient survival, procedural quality, subjective assessment of the HFMSM, and perceived workload. MAIN RESULTS: TM participants (N = 11) performed better than non-TM (NTM, N = 12) in providing expected care (accuracy), delivering care more consistently (reliability), and without consistent differences in efficiency (timeliness of care). Accuracy: TM completed 91% and NTM 42% of expected tasks and procedures. Efficiency: groups did not differ in the mean (± sd) minutes it took to obtain an advanced airway successfully (TM 15.2 ± 10.5 vs. NTM 22.8 ± 8.4, p = 0.10) or decompress a tension pneumothorax with a needle (TM 0.7 ± 0.5 vs. NTM 0.6 ± 0.9, p = 0.65). TM was slower than NTM in completing thoracostomy (22.3 ± 10.2 vs. 12.3 ± 4.8, p = 0.03). Reliability: TM performed 13 of 17 (76%) tasks with more consistent timing than NTM. TM completed 68% and NTM 29% of procedural quality metrics. Eighty-two percent of the TM participants versus 17% of the NTM participants simulated patients survived (p = 0.003). The groups similarly perceived the HFMSM as realistic, managed their patients with personal ownership, and experienced comparable workload and stress. CONCLUSIONS: Remote expertise provided with TM to caregivers in resource-limited settings improves caregiver performance, quality of care, and potentially real patient survival. HFMSM can be used to study interventions in ways not possible with real patients.

Asunto(s)

Cuidadores , Telemedicina , Humanos , Telemedicina/métodos , Cuidadores/educación , Cuidadores/psicología , Masculino , Femenino , Adulto , Competencia Clínica , Síndrome de Dificultad Respiratoria/terapia , Persona de Mediana Edad , Enfermedad Crítica , Reproducibilidad de los Resultados , Neumonía/terapia

RESUMEN

Community-acquired pneumonia continues to be one of the most common causes of morbidity and mortality due to infectious disease. The aetiologies, clinical presentations, diagnostic modalities and therapeutic options are changing and outpacing the creation of management guidelines. This educational article summarizes a roundtable activity sponsored by an unrestricted educational grant by Paratek that included US experts discussing these changes and identifying gaps in the current guidelines.

Asunto(s)

Infecciones Comunitarias Adquiridas , Neumonía , Guías de Práctica Clínica como Asunto , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Humanos , Estados Unidos , Neumonía/diagnóstico , Neumonía/terapia , Neumonía/tratamiento farmacológico , Antibacterianos/uso terapéutico