The unique metabolic and lipid profiles of patients with severe COVID-19 compared to severe community-acquired pneumonia: a potential prognostic and therapeutic target.

BACKGROUND: Compare the changes and differences in metabolome and lipidome profiles among severe COVID-19 and CAP patients with ARF to identify biomarkers that could be used for personalized diagnosis, prognosis, and treatment. RESEARCH DESIGN AND METHODS: Plasma samples were taken at hospital admission (baseline) and on the 5th day of hospitalization (follow-up) and examined by RP-LC-QTOF-MS and HILIC-LC-QTOF-MS. RESULTS: 127 patients, 17 with CAP and 110 with COVID-19, were included. The analysis revealed 87 altered metabolites, suggesting changes in the metabolism of arachidonic acid, glycerolipids, glycerophospholipids, linoleic acid, pyruvate, glycolysis, among others. Most of these metabolites are involved in inflammatory, hypoxic, and thrombotic processes. At baseline, the greatest differences were found in phosphatidylcholine (PC) 31:4 (p < 0.001), phosphoserine (PS) 34:3 (p < 0.001), and phosphatidylcholine (PC) 36:5 (p < 0.001), all of which were notably decreased in COVID-19 patients. At follow-up, the most dysregulated metabolites were monomethyl-phosphatidylethanolamine (PE-Nme) 40:5 (p < 0.001) and phosphatidylcholine (PC) 38:4 (p < 0.001). CONCLUSIONS: Metabolic and lipidic alterations suggest inhibition of innate anti-inflammatory and anti-thrombotic mechanisms in COVID-19 patients, which might lead to increased viral proliferation, uncontrolled inflammation, and thrombi formation. Results provide novel targets for predictive biomarkers against CAP and COVID-19. TRIAL REGISTRATION: Not applicable.

Improving Antibiotic Prescribing for Children with Community-acquired Pneumonia in Outpatient Settings.

OBJECTIVE: To assess whether a two-phase intervention was associated with improvements in antibiotic prescribing among nonhospitalized children with community-acquired pneumonia. STUDY DESIGN: In a large health care organization, a first intervention phase was implemented in September 2020 directed at antibiotic choice and duration for children 2 months through 17 years of age with pneumonia. Activities included clinician education and implementation of a pneumonia-specific order set in the electronic health record. In October 2021, a second phase comprised additional education and order set revisions. A narrow spectrum antibiotic (eg, amoxicillin) was recommended in most circumstances. Electronic health record data were used to identify pneumonia cases and antibiotics ordered. Using interrupted time series analyses, antibiotic choice and duration after phase one (September 2020-September 2021) and after phase two (October 2021-October 2022) were compared with a preintervention prepandemic period (January 2016-early March 2020). RESULTS: Overall, 3570 cases of community-acquired pneumonia were identified: 3246 cases preintervention, 98 post-phase one, and 226 post-phase two. The proportion receiving narrow spectrum monotherapy increased from 40.6% preintervention to 68.4% post-phase one to 69.0% post-phase two (P < .001). For children with an initial narrow spectrum antibiotic, duration decreased from preintervention (mean duration 9.9 days, SD 0.5 days) to post-phase one (mean 8.2, SD 1.9) to post-phase two (mean 6.8, SD 2.3) periods (P < .001). CONCLUSIONS: A two-phase intervention with educational sessions combined with clinical decision support was associated with sustained improvements in antibiotic choice and duration among children with community-acquired pneumonia.

A targeted likelihood estimation comparing cefepime and piperacillin/tazobactam in critically ill patients with community-acquired pneumonia (CAP).

Cefepime and piperacillin/tazobactam are antimicrobials recommended by IDSA/ATS guidelines for the empirical management of patients admitted to the intensive care unit (ICU) with community-acquired pneumonia (CAP). Concerns have been raised about which should be used in clinical practice. This study aims to compare the effect of cefepime and piperacillin/tazobactam in critically ill CAP patients through a targeted maximum likelihood estimation (TMLE). A total of 2026 ICU-admitted patients with CAP were included. Among them, (47%) presented respiratory failure, and (27%) developed septic shock. A total of (68%) received cefepime and (32%) piperacillin/tazobactam-based treatment. After running the TMLE, we found that cefepime and piperacillin/tazobactam-based treatments have comparable 28-day, hospital, and ICU mortality. Additionally, age, PTT, serum potassium and temperature were associated with preferring cefepime over piperacillin/tazobactam (OR 1.14 95% CI [1.01-1.27], p = 0.03), (OR 1.14 95% CI [1.03-1.26], p = 0.009), (OR 1.1 95% CI [1.01-1.22], p = 0.039) and (OR 1.13 95% CI [1.03-1.24], p = 0.014)]. Our study found a similar mortality rate among ICU-admitted CAP patients treated with cefepime and piperacillin/tazobactam. Clinicians may consider factors such as availability and safety profiles when making treatment decisions.

Community-acquired pneumonia associated with immunosuppression due to follicular thyroid cancer: a case report.

BACKGROUND: We present the case of a woman with cancer, which weakened the immune system and increased the risk of infection. Thus, infections are a frequent complication of cancer. The development of community-acquired pneumonia, an acute respiratory infectious disease that damages the lung parenchyma, caused by the invasion of pathogenic microorganisms, can lead to respiratory failure with multiorgan failure due to respiratory sepsis. CASE PRESENTATION: Case report of a 38-year-old mixed-race woman with diabetes mellitus and irregular treatment, who was admitted with community-acquired pneumonia complicated by type I respiratory failure requiring mechanical ventilation. During her hospital stay, she developed ventilator-associated pneumonia, recurrent empyema, bronchopleural fistula, refractory septic shock and multiorgan dysfunction despite multiple interventions. The patient required prolonged mechanical ventilation, vasopressor support and antibiotic therapy. After 62 days, metastatic papillary thyroid carcinoma was diagnosed. She presented with hypoparathyroidism and permanent hypocalcemia. She died after multiple complications and a refractory critical condition. CONCLUSION: The case exemplifies the potential severity of community-acquired pneumonia in a patient with risk factors such as diabetes and immunosuppression. It highlights the complexity of treating multiple comorbidities and the importance of multidisciplinary management with close surveillance for timely interventions for complications.

Chlamydia psittaci-related pleuro-myocarditis.

Chlamydia psittaci ‒ related community-acquired pneumonia associated to acute myocarditis was diagnosed in a young man with no medical history, and a professional exposition to birds. The diagnosis was confirmed with positive specific polymerase chain reaction in bronchoalveolar lavage. The patient was treated with spiramycin for two weeks with anti-inflammatory treatment for myocarditis for three months. Clinical and biological improvement was rapidly observed followed by normalization of electrocardiogram and chest CT scan. No relapse was reported for over a two-year follow-up.

Clinical and Epidemiological Assessment of Children and Adolescents Hospitalized with SARS-CoV-2 in the Pre-Amazon Region.

INTRODUCTION: SARS-CoV-2 infection usually presents similarly to other respiratory viral pathogens. Children and adolescents do not present as a group that is highly affected by the disease, having low infection rates. However, limited publications are associated with the findings of pneumonia in pediatric patients with COVID-19. OBJECTIVE: To analyze the clinical and epidemiological aspects of children and adolescents hospitalized with SARS-CoV-2 in a pre-Amazon region. METHODS: A retrospective study, carried out in four public hospitals in São Luís, Brazil where medical records of children and adolescents aged from 0 to 13 years, of both sexes, with clinical diagnosis of community-acquired pneumonia were evaluated from March 2020 to March 2021. RESULTS: Almost 40.0% of children were aged between 1 year and 5 years. Of the 128 children who had SARS-CoV-2, 3 are of indigenous ethnicity. Additionally, 78.6% of the children had fever and there was no significant difference between COVID-19 patients and those of other respiratory viruses. Eighteen patients had chronic neurological disease, which is the most common comorbidity observed in patients with coronavirus infection. Ground glass opacity attenuation was observed in 24.8% of children and adolescents with COVID-19. Anemia and increased inflammatory response markers were related to SARS-CoV-2 infection. More than 90.0% of patients admitted to hospital, regardless of etiology, were treated with antibiotics. Eighteen patients died. Pediatric multisystem inflammatory syndrome (PMIS) was diagnosed in 17 patients. CONCLUSIONS: SARS-CoV-2 in children and adolescents is mild, but the condition of patients with PMIS is more serious, with an increase in inflammatory biomarkers which can lead to death. Therefore, rapid diagnosis and differentiation of agents causing respiratory diseases are necessary for better therapeutic decision making, since the results of this study make us question the excessive use of antibiotics without meeting well-defined clinical-epidemiological criteria.

Challenges for a broad international implementation of the current severe community-acquired pneumonia guidelines.

Severe community-acquired pneumonia (sCAP) remains one of the leading causes of admission to the intensive care unit, thus consuming a large share of resources and is associated with high mortality rates worldwide. The evidence generated by clinical studies in the last decade was translated into recommendations according to the first published guidelines focusing on severe community-acquired pneumonia. Despite the advances proposed by the present guidelines, several challenges preclude the prompt implementation of these diagnostic and therapeutic measures. The present article discusses the challenges for the broad implementation of the sCAP guidelines and proposes solutions when applicable.

Derivación y validación de un nuevo puntaje predictivo de mortalidad por covid-19 en la altura / Derivation and Validation of a New covid-19 Predictive Score for Mortality at High Altitude / Derivação e validação de um novo escore preditivo de mortalidade por covid-19 em altitude

Objetivo: desarrollar un puntaje predictivo de mortalidad para pacientes con covid-19. Materiales y méto-dos: estudio retrospectivo, analítico, observacional y transversal, realizado en dos fases. Se revisaron 620 historias clínicas con una cohorte de derivación de 320 pacientes y una de validación de 300 pacientes. Las variables se analizaron con test de Anova, chi cuadrado de Pearson y análisis multivariante con regresión binaria, que determinaron sensibilidad, especificidad y valor predictivo negativo y positivo. Los puntajes se compararon mediante curvas cor con los scoresnews y hews. Resultados: los dos puntajes obtenidos incluyeron valores de edad, conteo de linfocitos, SatO2/FiO2, leucocitos, plaquetas, ausencia de síntomas, hipertensión arterial, epid y dhl. El área bajo la curva (abc) fue de 0.838 para el puntaje con dhl, con una mortalidad del 100 % para 7.75 puntos o más, y un abc de 0.826 para el primer puntaje. En la cohorte de validación, el abc para el primer puntaje fue de 0.831 y para el score con dhl fue 0.855. El puntaje hewsobtuvo un abc de 0.451, y el news, un abc de 0.396. Conclusiones: se desarrollaron dos herramientas para predecir mortalidad en pacientes con covid-19, con alto poder de discriminación, superior a los puntajes británicos hews y news

Objetivo: desarrollar un puntaje predictivo de mortalidad para pacientes con covid-19. Materiales y méto-dos: estudio retrospectivo, analítico, observacional y transversal, realizado en dos fases. Se revisaron 620 historias clínicas con una cohorte de derivación de 320 pacientes y una de validación de 300 pacientes. Las variables se analizaron con test de Anova, chi cuadrado de Pearson y análisis multivariante con regresión binaria, que determinaron sensibilidad, especificidad y valor predictivo negativo y positivo. Los puntajes se compararon mediante curvas cor con los scoresnews y hews. Resultados: los dos puntajes obtenidos incluyeron valores de edad, conteo de linfocitos, SatO2/FiO2, leucocitos, plaquetas, ausencia de síntomas, hipertensión arterial, epid y dhl. El área bajo la curva (abc) fue de 0.838 para el puntaje con dhl, con una mortalidad del 100 % para 7.75 puntos o más, y un abc de 0.826 para el primer puntaje. En la cohorte de validación, el abc para el primer puntaje fue de 0.831 y para el score con dhl fue 0.855. El puntaje hewsobtuvo un abc de 0.451, y el news, un abc de 0.396. Conclusiones: se desarrollaron dos herramientas para predecir mortalidad en pacientes con covid-19, con alto poder de discriminación, superior a los puntajes británicos hews y news

Objetivo: desenvolver um escore preditivo de mortalidade para pacientes com covid-19. Materiais e Métodos: estudo retrospectivo, analítico, observacional e transversal, realizado em duas fases. Foram revisados 620 prontuários, com uma coorte de derivação de 320 pacientes e uma coorte de validação de 300 pacientes. As variáveis foram analisadas com teste anova, qui-quadrado de Pearson e análise multivariada com regressão binária, determinando sensibilidade, especificidade, valor preditivo nega-tivo e positivo. As pontuações foram comparadas por meio de curvas cor com as pontuações news e hews. Resultados: os dois escores obtidos incluíram valores de: idade, contagem de linfócitos, SatO2/FiO2, leucócitos, plaquetas, ausência de sintomas, hipertensão arterial, epid e dhl. A área sob a curva (abc) foi de 0,838 para o escore dhl, com 100 % de mortalidade para 7,75 pontos ou mais, e uma abc de 0,826 para o primeiro escore. Na coorte de validação, a abc para o primeiro escore foi de 0,831 e para o escore com dhl foi de 0,855. A pontuação hews obteve abc de 0,451 e o news uma abc de 0,396. Conclusões: foram desenvolvidas duas ferramentas para prever mortalidade em pacientes com covid-19, com alto poder de discriminação, superior aos escores britânicos hews e news

Chlamydia psittaci—related pleuro-myocarditis

ABSTRACT Chlamydia psittaci - related community-acquired pneumonia associated to acute myocarditis was diagnosed in a young man with no medical history, and a professional exposition to birds. The diagnosis was confirmed with positive specific polymerase chain reaction in bronchoalveolar lavage. The patient was treated with spiramycin for two weeks with anti-inflammatory treatment for myocarditis for three months. Clinical and biological improvement was rapidly observed followed by normalization of electrocardiogram and chest CT scan. No relapse was reported for over a two-year follow-up.

Investigation of etiology of community-acquired pneumonia in hospitalized patients in a tertiary hospital of São Paulo City, Brazil.

BACKGROUND: Community-Acquired Pneumonia (CAP) is the primary cause of hospitalization in the United States and the third leading cause of death in Brazil. The gold standard for diagnosing the etiology of CAP includes blood culture, Gram-stained sputum, and sputum culture. However, these methods have low sensitivity. No studies investigating the etiology of CAP have been conducted in Brazil in the last 20-years, and the empirical choice of antimicrobials is mainly based on the IDSA guidelines. This is the first national study with this aim, and as a result, there's potential for the Brazilian consensus to be impacted and possibly modify its guidelines rather than adhering strictly to the IDSA's recommendations. METHODS: The aim of this study is to identify the main microorganisms implicated in CAP by employing a multiplex Polymerase Chain Reaction (mPCR) at the foremost public hospital in Brazil. All patients who were admitted to the emergency department and diagnosed with severe CAP underwent an mPCR panel using nasopharyngeal and oropharyngeal swabs, with the aim of detecting 13 bacterial and 21 viral pathogens. RESULTS: A total of 169 patients were enrolled in the study. The mPCR panel identified an etiological agent in 61.5% of patients, with viruses being the most common (42.01%), led by Rhinovirus, followed by Influenza and Coronavirus (non-SARS-CoV-2). Bacterial agents were identified in 34.91% of patients, with S. pneumoniae being the most common, followed by H. influenzae, M. catarrhalis, and S. aureus. Additionally, we found that the prescription for 92.3% of patients could be modified, with most changes involving de-escalation of antibiotics and antiviral therapy. CONCLUSION: Our study revealed different etiological causes of CAP than those suggested by the Brazilian guidelines. Using molecular diagnostic tests, we were able to optimize treatment by using fewer antibiotics.

A Systematic Review of Gene Expression Studies in Critically Ill Patients with Sepsis and Community-Acquired Pneumonia.

(1) Background: Sepsis is present in nearly 90% of critically ill patients with community-acquired pneumonia (CAP). This systematic review updates the information on studies that have assessed gene expression profiles in critically ill septic patients with CAP. (2) Methods: We searched for studies that satisfied the following criteria: (a) expression profile in critically ill patients with sepsis due to CAP, (b) presence of a control group, and (c) adult patients. Over-representation analysis was performed with clusterProfiler using the Hallmark and Reactome collections. (3) Results: A total of 4312 differentially expressed genes (DEGs) and sRNAs were included in the enrichment analysis. In the Hallmark collection, genes regulated by nuclear factor kappa B in response to tumor necrosis factor, genes upregulated by signal transducer and activator of transcription 5 in response to interleukin 2 stimulation, genes upregulated in response to interferon-gamma, genes defining the inflammatory response, a subgroup of genes regulated by MYC-version 1 (v1), and genes upregulated during transplant rejection were significantly enriched in critically ill septic patients with CAP. Moreover, 88 pathways were identified in the Reactome database. (4) Conclusions: This study summarizes the reported DEGs in critically ill septic patients with CAP and investigates their functional implications. The results highlight the complexity of immune responses during CAP.

Fisioterapia respiratoria en sujetos adultos cursando internación por neumonía adquirida en la comunidad. Revisión bibliográfica

Introducción: La neumonía adquirida en la comunidad (NAC) es una infección respiratoria en la cual es frecuente observar la indicación de fisioterapia respiratoria (FR). Sin embargo, en la actualidad las recomendaciones respecto a su uso en NAC son controvertidas, no existiendo evidencia que respalde su uso y permita conocer su real alcance. Objetivos: Revisar la evidencia respecto al impacto de la FR en pacientes adultos que cursan internación por NAC. Resultados: 5 estudios cumplieron los criterios de inclusión de esta revisión. Las maniobras de FR incluyeron ejercicios respiratorios, drenaje postural, percusión, vibración, espirometría incentivada, resistencia espiratoria, asistencia torácica durante movimientos respiratorios, tos dirigida y presión positiva intermitente. En los estudios incluidos la FR no disminuyó la mortalidad ni mejoró los valores espirométricos en los pacientes con NAC, así como tampoco los días hasta la curación ni la estadía hospitalaria. Respecto a los costos, el uso de FR en pacientes con NAC presentó un incremento significativo de los mismos. Conclusión: No hay evidencia que respalde el uso de manera rutinaria de FR en los pacientes adultos con NAC. Consideramos que se requieren de futuras investigaciones que permitan conocer el impacto de la FR en pacientes adultos con NAC, así como establecer consensos respecto a su indicación, selección de maniobras, estandarización de técnicas, tiempos y dosificación.

Introduction: Community-acquired pneumonia (CAP) is a respiratory infection in which the indication for respiratory physiotherapy (RF) is frequently observed. However, currently the recommendations regarding its use in CAP are controversial, and there is no evidence to support its use and allow us to know its real scope. Objectives: To review the evidence regarding the impact of RF in adult patients who are hospitalized for CAP. Results: 5 studies met the inclusion criteria of this review. RF maneuvers included breathing exercises, postural drainage, percussion, vibration, incentive spirometry, expiratory resistance, chest support during respiratory movements, directed cough, and intermittent positive pressure. In the included studies, RF did not reduce mortality or improve spirometric values in patients with CAP, nor did it improve days to cure or hospital stay. Regarding costs, the use of RF in patients with CAP presented a significant increase in costs. Conclusion: There is no evidence to support the routine use of RF in adult patients with CAP. We believe that future research is required to determine the impact of RF in adult patients with CAP, as well as to establish consensus regarding its indication, selection of maneuvers, standardization of techniques, times, and dosage.

Fisioterapia respiratoria en sujetos adultos cursando internación por neumonía adquirida en la comunidad. Revisión bibliográfica / Respiratory physiotherapy in adult subjects hospitalized for community-acquired pneumonia. Literature review

Introducción: La neumonía adquirida en la comunidad (NAC) es una infección respiratoria en la cual es frecuente observar la indicación de fisioterapia respiratoria (FR). Sin embargo, en la actualidad las recomendaciones respecto a su uso en NAC son controvertidas, no existiendo evidencia que respalde su uso y permita conocer su real alcance. Objetivos: Revisar la evidencia respecto al impacto de la FR en pacientes adultos que cursan internación por NAC. Resultados: 5 estudios cumplieron los criterios de inclusión de esta revisión. Las maniobras de FR incluyeron ejercicios respiratorios, drenaje postural, percusión, vibración, espirometría incentivada, resistencia espiratoria, asistencia torácica durante movimientos respiratorios, tos dirigida y presión positiva intermitente. En los estudios incluidos la FR no disminuyó la mortalidad ni mejoró los valores espirométricos en los pacientes con NAC, así como tampoco los días hasta la curación ni la estadía hospitalaria. Respecto a los costos, el uso de FR en pacientes con NAC presentó un incremento significativo de los mismos. Conclusión: No hay evidencia que respalde el uso de manera rutinaria de FR en los pacientes adultos con NAC. Consideramos que se requieren de futuras investigaciones que permitan conocer el impacto de la FR en pacientes adultos con NAC, así como establecer consensos respecto a su indicación, selección de maniobras, estandarización de técnicas, tiempos y dosificación.

Introduction: Community-acquired pneumonia (CAP) is a respiratory infection in which the indication for respiratory physiotherapy (RF) is frequently observed. However, currently the recommendations regarding its use in CAP are controversial, and there is no evidence to support its use and allow us to know its real scope. Objectives: To review the evidence regarding the impact of RF in adult patients who are hospitalized for CAP. Results: 5 studies met the inclusion criteria of this review. RF maneuvers included breathing exercises, postural drainage, percussion, vibration, incentive spirometry, expiratory resistance, chest support during respiratory movements, directed cough, and intermittent positive pressure. In the included studies, RF did not reduce mortality or improve spirometric values in patients with CAP, nor did it improve days to cure or hospital stay. Regarding costs, the use of RF in patients with CAP presented a significant increase in costs. Conclusion: There is no evidence to support the routine use of RF in adult patients with CAP. We believe that future research is required to determine the impact of RF in adult patients with CAP, as well as to establish consensus regarding its indication, selection of maneuvers, standardization of techniques, times, and dosage.

Lung microbiome and origins of the respiratory diseases.

The studies on the composition of the human microbiomes in healthy individuals, its variability in the course of inflammation, infection, antibiotic therapy, diets and different pathological conditions have revealed their intra and inter-kingdom relationships. The lung microbiome comprises of major species members of the phylum Bacteroidetes, Firmicutes, Actinobacteria, Fusobacteria and Proteobacteria, which are distributed in ecological niches along nasal cavity, nasopharynx, oropharynx, trachea and in the lungs. Commensal and pathogenic species are maintained in equilibrium as they have strong relationships. Bacterial overgrowth after dysbiosis and/or imbalanced of CD4+ helper T cells, CD8+ cytotoxic T cells and regulatory T cells (Treg) populations can promote lung inflammatory reactions and distress, and consequently acute and chronic respiratory diseases. This review is aimed to summarize the latest advances in resident lung microbiome and its participation in most common pulmonary infections and pneumonia, community-acquired pneumonia (CAP), ventilator-associated pneumonia (VAP), immunodeficiency associated pneumonia, SARS-CoV-2-associated pneumonia, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). We briefly describe physiological and immunological mechanisms that selectively create advantages or disadvantages for relative growth of pathogenic bacterial species in the respiratory tract. At the end, we propose some directions and analytical methods that may facilitate the identification of key genera and species of resident and transient microbes involved in the respiratory diseases' initiation and progression.

Impact of macrolide treatment on long-term mortality in patients admitted to the ICU due to CAP: a targeted maximum likelihood estimation and survival analysis.

INTRODUCTION: Patients with community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU) have high mortality rates during the acute infection and up to ten years thereafter. Recommendations from international CAP guidelines include macrolide-based treatment. However, there is no data on the long-term outcomes of this recommendation. Therefore, we aimed to determine the impact of macrolide-based therapy on long-term mortality in this population. METHODS: Registered patients in the MIMIC-IV database 16 years or older and admitted to the ICU due to CAP were included. Multivariate analysis, targeted maximum likelihood estimation (TMLE) to simulate a randomised controlled trial, and survival analyses were conducted to test the effect of macrolide-based treatment on mortality six-month (6 m) and twelve-month (12 m) after hospital admission. A sensitivity analysis was performed excluding patients with Pseudomonas aeruginosa or MRSA pneumonia to control for Healthcare-Associated Pneumonia (HCAP). RESULTS: 3775 patients were included, and 1154 were treated with a macrolide-based treatment. The non-macrolide-based group had worse long-term clinical outcomes, represented by 6 m [31.5 (363/1154) vs 39.5 (1035/2621), p < 0.001] and 12 m mortality [39.0 (450/1154) vs 45.7 (1198/2621), p < 0.001]. The main risk factors associated with long-term mortality were Charlson comorbidity index, SAPS II, septic shock, and respiratory failure. Macrolide-based treatment reduced the risk of dying at 6 m [HR (95% CI) 0.69 (0.60, 0.78), p < 0.001] and 12 m [0.72 (0.64, 0.81), p < 0.001]. After TMLE, the protective effect continued with an additive effect estimate of - 0.069. CONCLUSION: Macrolide-based treatment reduced the hazard risk of long-term mortality by almost one-third. This effect remains after simulating an RCT with TMLE and the sensitivity analysis for the HCAP classification.

Whole-Blood Gene Expression Profiles Associated with Mortality in Community-Acquired Pneumonia.

(1) Background: Information regarding gene expression profiles and the prognosis of community-acquired pneumonia (CAP) is scarce. We aimed to examine the differences in the gene expression profiles in peripheral blood at hospital admission between patients with CAP who died during hospitalization and those who survived. (2) Methods: This is a multicenter study of nonimmunosuppressed adult patients who required hospitalization for CAP. Whole blood samples were obtained within 24 h of admission for genome-expression-profile analysis. Gene expression profiling identified both differentially expressed genes and enriched gene sets. (3) Results: A total of 198 samples from adult patients who required hospitalization for CAP were processed, of which 13 were from patients who died. Comparison of gene expression between patients who died and those who survived yielded 49 differentially expressed genes, 36 of which were upregulated and 13 downregulated. Gene set enrichment analysis (GSEA) identified four positively enriched gene sets in survivors, mainly associated with the interferon-alpha response, apoptosis, and sex hormone pathways. Similarly, GSEA identified seven positively enriched gene sets, associated with the oxidative stress, endoplasmic reticulum stress, oxidative phosphorylation, and angiogenesis pathways, in the patients who died. Protein-protein-interaction-network analysis identified FOS, CDC42, SLC26A10, EIF4G2, CCND3, ASXL1, UBE2S, and AURKA as the main gene hubs. (4) Conclusions: We found differences in gene expression profiles at hospital admission between CAP patients who died and those who survived. Our findings may help to identify novel candidate pathways and targets for potential intervention and biomarkers for risk stratification.

Comparison of systemic inflammatory profiles in COVID-19 and community-acquired pneumonia patients: a prospective cohort study.

BACKGROUND: Inflammatory responses contribute to tissue damage in COVID-19 and community-acquired pneumonia (CAP). Although predictive values of different inflammatory biomarkers have been reported in both, similarities and differences of inflammatory profiles between these conditions remain uncertain. Therefore, we aimed to determine the similarities and differences of the inflammatory profiles between COVID-19 and CAP, and their association with clinical outcomes. METHODS: We report a prospective observational cohort study; conducted in a reference hospital in Latin America. Patients with confirmed COVID-19 pneumonia and CAP were included. Multiplex (Luminex) cytokine assays were used to measure the plasma concentration of 14 cytokines at hospital admission. After comparing similarities and differences in the inflammatory profile between COVID-19 and CAP patients, an unsupervised classification method (i.e., hierarchical clustering) was used to identify subpopulations within COVID-19 and CAP patients. RESULTS: A total of 160 patients were included, 62.5% were diagnosed with COVID-19 (100/160), and 37.5% with CAP (60/160). Using the hierarchical clustering, COVID-19 and CAP patients were divided based on its inflammatory profile: pauci, moderate, and hyper-inflammatory immune response. COVID-19 hyper-inflammatory subpopulation had the highest mortality. COVID-19 hyper-inflammatory subpopulation, compared to pauci-inflammatory, had higher levels of IL-10 (median [IQR] 61.4 [42.0-109.4] vs 13.0 [5.0-24.9], P: < 0.001), IL-6 (48.1 [22.3-82.6] vs 9.1 [0.1-30.4], P: < 0.001), among others. Hyper-inflammatory vs pauci-inflammatory CAP patients were characterized by elevation of IFN2 (48.8 [29.7-110.5] vs 3.0 [1.7-10.3], P: < 0.001), TNFα (36.3 [24.8-53.4] vs 13.1 [11.3-16.9], P: < 0.001), among others. Hyper-inflammatory subpopulations in COVID-19 and CAP compared to the corresponding pauci-inflammatory subpopulations had higher MCP-1. CONCLUSIONS: Our data highlights three distinct subpopulations in COVID-19 and CAP, with differences in inflammatory marker profiles and risks of adverse clinical outcomes. TRIAL REGISTRATION: This is a prospective study, therefore no health care intervention were applied to participants and trial registration is not applicable.

Bula gigante secundaria a neumonía adquirida en la comunidad en niños / Giant Bulla Secondary to Community-Acquired Pneumonia in Children

Introducción: Los neumatoceles y las bulas pulmonares son lesiones que se observan en los niños casi siempre asociadas a neumonías infecciosas, aunque sus causas pueden ser diversas. La importancia clínica de estos procesos radica en el peligro de crecimiento progresivo, que puede comprometer las funciones respiratoria y cardiovascular. Objetivo: Describir las experiencias derivadas del proceso de diagnóstico por imágenes y del tratamiento invasivo de casos atendidos. Presentación de los casos: Desde finales de 2021 y durante un período de un año, se atendieron, en la unidad de cuidados intensivos pediátricos del Hospital Pediátrico Universitario de Cienfuegos, cinco niños con neumonías extensas, que desarrollaron bulas de gran tamaño varios días después del tratamiento antimicrobiano adecuado. Estas necesitaron drenaje y aspiración percutáneos debido a su magnitud y a la presencia de síntomas cardiovasculares. Conclusiones: Las bulas que aparecieron como complicación de la neumonía en el niño pueden presentarse con una frecuencia no despreciable, y hay que mantenerse atentos a su evolución, porque, a diferencia de los neumatoceles, pueden crecer progresivamente y comprometer las funciones respiratoria y cardiovascular. El drenaje percutáneo y aspiración continua por cinco días resultó un método seguro y eficaz para tratar estos procesos(AU)

Introduction: Pneumoatoceles and pulmonary bullae are lesions that are observed in children almost always associated with infectious pneumonia, although their causes may be diverse. The clinical importance of these processes lies in the danger of progressive growth, which can compromise respiratory and cardiovascular functions. Objective: To describe the experiences derived from the imaging process and the invasive treatment of treated cases. Presentation of the cases: Since the end of 2021 and for a period of one year, five children with extensive pneumonia were treated in the pediatric intensive care unit of the University Pediatric Hospital of Cienfuegos, who developed large bullae several days after appropriate antimicrobial treatment. The bullae required percutaneous drainage and aspiration due to their magnitude and the presence of cardiovascular symptoms. Conclusions: The bulla that appeared as a complication of pneumonia in the child can occur with a not negligible frequency, and it is necessary to be attentive to their evolution, because, unlike pneumoatoceles, can grow progressively and compromise respiratory and cardiovascular functions. Percutaneous drainage and continuous aspiration for five days was a safe and effective method to treat these processes(AU)

Investigation of etiology of community-acquired pneumonia in hospitalized patients in a tertiary hospital of São Paulo City, Brazil

Abstract Background Community-Acquired Pneumonia (CAP) is the primary cause of hospitalization in the United States and the third leading cause of death in Brazil. The gold standard for diagnosing the etiology of CAP includes blood culture, Gram-stained sputum, and sputum culture. However, these methods have low sensitivity. No studies investigating the etiology of CAP have been conducted in Brazil in the last 20-years, and the empirical choice of antimicrobials is mainly based on the IDSA guidelines. This is the first national study with this aim, and as a result, there's potential for the Brazilian consensus to be impacted and possibly modify its guidelines rather than adhering strictly to the IDSA's recommendations. Methods The aim of this study is to identify the main microorganisms implicated in CAP by employing a multiplex Polymerase Chain Reaction (mPCR) at the foremost public hospital in Brazil. All patients who were admitted to the emergency department and diagnosed with severe CAP underwent an mPCR panel using nasopharyngeal and oropharyngeal swabs, with the aim of detecting 13 bacterial and 21 viral pathogens. Results A total of 169 patients were enrolled in the study. The mPCR panel identified an etiological agent in 61.5% of patients, with viruses being the most common (42.01%), led by Rhinovirus, followed by Influenza and Coronavirus (non-SARS-CoV-2). Bacterial agents were identified in 34.91% of patients, with S. pneumoniae being the most common, followed by H. influenzae, M. catarrhalis, and S. aureus. Additionally, we found that the prescription for 92.3% of patients could be modified, with most changes involving de-escalation of antibiotics and antiviral therapy. Conclusion Our study revealed different etiological causes of CAP than those suggested by the Brazilian guidelines. Using molecular diagnostic tests, we were able to optimize treatment by using fewer antibiotics.

Intervención educativa sobre las neumonías extrahospitalarias en el adulto mayor. Policlínico Docente Mario Muñoz Monroy. 2019-2020

Introducción: las neumonías extrahospitalarias en el anciano son un problema de salud mundial en el marco del envejecimiento poblacional, lo que hace necesario su prevención y diagnóstico precoz. Objetivo: implementar una estrategia de intervención educativa dirigida a elevar los conocimientos sobre el tema, en adultos mayores de 60 años del Consultorio no. 27 del Policlínico Docente Mario Muñoz Monroy. Materiales y métodos: se realizó un estudio cuasiexperimental de tipo intervención educativa, en el municipio Rafael Freyre, de la provincia de Holguín, entre enero de 2019 y diciembre de 2020. Se trabajó con una muestra de 50 representantes de la comunidad, seleccionados de modo intencional, en los que se indagó su nivel de información sobre el tema antes y después de aplicar la intervención educativa. El método estadístico utilizado fue la prueba de McNemar, utilizando el paquete estadístico SPSS. Resultados: los conocimientos sobre los síntomas y signos de las neumonías extrahospitalarias que fueron evaluados de bueno, se incrementaron de 18 a 80 %, y sobre las medidas preventivas los resultados fueron de 22 a 94 %. El indicador con mejores resultados fue factores de riesgo, donde el valor de la escala de bueno aumentó a 96 % tras la intervención. Conclusiones: la intervención educativa aplicada con la finalidad de elevar los conocimientos de los pacientes mayores de 60 años del Consultorio no. 27 del Policlínico Docente Mario Muñoz Monroy, posibilitó enriquecer su conocimiento sobre las neumonías extrahospitalarias.

Introduction: community-acquired pneumonia in the elderly is a global health problem in the context of population aging, which makes its prevention and early diagnosis necessary. Objective: to implement an educational intervention strategy aimed at increasing knowledge on the subject in elder people over 60 years from the Doctor's Office nr. 27 of the Mario Munoz Monroy Teaching Polyclinic. Materials and methods: a quasi-experimental study of educational intervention type was conducted in the municipality Rafael Freyre, in the province of Holguin, between January 2019 and December 2020. A sample of 50 community representatives, intentionally selected, was worked on to investigate their level of information on the subject before and after applying the educational intervention. The statistical method used was the McNemar's test, using the SPSS statistical package. Results: the knowledge on the symptoms and signs of community-acquired pneumonias that were evaluated as good, increased from 18 to 80%, and on preventive measures the results increased from 22 to 94%. The indicator with the best results was risk factors, where the good value of the scale increased to 96% after the intervention. Conclusions: the educational intervention applied with the aim of increasing the knowledge of patients over 60 years of age from the Doctor's Office nr. 27 of the Mario Muñoz Monroy Teaching Polyclinic, made it possible to enrich their knowledge about community-acquired pneumonias.