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The World Health Organization's end TB strategy promotes the use of symptom and chest radiograph screening for tuberculosis (TB) disease. However, asymptomatic early states of TB beyond latent TB infection and active disease can go unrecognized using current screening criteria. We conducted a longitudinal cohort study enrolling household contacts initially free of TB disease and followed them for the occurrence of incident TB over 1 year. Among 1,747 screened contacts, 27 (52%) of the 52 persons in whom TB subsequently developed during follow-up had a baseline abnormal radiograph. Of contacts without TB symptoms, persons with an abnormal radiograph were at higher risk for subsequent TB than persons with an unremarkable radiograph (adjusted hazard ratio 15.62 [95% CI 7.74-31.54]). In young adults, we found a strong linear relationship between radiograph severity and time to TB diagnosis. Our findings suggest chest radiograph screening can extend to detecting early TB states, thereby enabling timely intervention.
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Composición Familiar , Tamizaje Masivo , Radiografía Torácica , Humanos , Perú/epidemiología , Masculino , Femenino , Adulto , Adolescente , Adulto Joven , Tamizaje Masivo/métodos , Estudios Longitudinales , Persona de Mediana Edad , Niño , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/diagnóstico por imagen , Trazado de Contacto/métodos , Preescolar , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/diagnóstico por imagen , Lactante , Tuberculosis/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/diagnóstico por imagenRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected individuals worldwide, and patients with cancer are particularly vulnerable to COVID-19-related severe illness, respiratory failure, and mortality. The relationship between COVID-19 and cancer remains a critical concern, and a comprehensive investigation of the factors affecting survival among patients with cancer who develop COVID-19-related respiratory failure is warranted. We aim to compare the characteristics and outcomes of COVID-19-related acute respiratory failure in patients with and without underlying cancer, while analyzing factors affecting in-hospital survival among cancer patients. METHODS: We conducted a retrospective observational study at Taipei Veterans General Hospital in Taiwan from May to September 2022, a period during which the omicron variant of the severe acute respiratory syndrome coronavirus 2 was circulating. Eligible patients had COVID-19 and acute respiratory failure. Clinical data, demographic information, disease severity markers, treatment details, and outcomes were collected and analyzed. RESULTS: Of the 215 enrolled critically ill patients with COVID-19, 65 had cancer. The patients with cancer were younger and had lower absolute lymphocyte counts, higher ferritin and lactate dehydrogenase (LDH) concentrations, and increased vasopressor use compared with those without cancer. The patients with cancer also received more COVID-19 specific treatments but had higher in-hospital mortality rate (61.5% vs 36%, P = 0.002) and longer viral shedding (13 vs 10 days, P = 0.007) than those without cancer did. Smoking [odds ratio (OR): 5.804, 95% confidence interval (CI): 1.847-39.746], elevated LDH (OR: 1.004, 95% CI: 1.001-1.012), vasopressor use (OR: 5.437, 95% CI: 1.202-24.593), and new renal replacement therapy (OR: 3.523, 95% CI: 1.203-61.108) were independent predictors of in-hospital mortality among patients with cancer and respiratory failure. CONCLUSION: Critically ill patients with cancer experiencing COVID-19-related acute respiratory failure present unique clinical features and worse clinical outcomes compared with those without cancer. Smoking, elevated LDH, vasopressor use, and new renal replacement therapy were risk factors for in-hospital mortality in these patients.
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COVID-19 , Neoplasias , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Humanos , COVID-19/complicaciones , SARS-CoV-2 , Enfermedad Crítica , Neoplasias/complicaciones , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Estudios RetrospectivosRESUMEN
BACKGROUND/PURPOSE: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is common in critically ill patients with COVID-19 and is associated with worse outcomes. However, reports on CAPA and its impact on treatment outcomes in Asian populations are limited. METHODS: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction-confirmed COVID-19 admitted to intensive care units (ICUs) were retrospectively enrolled in this observational study. The incidence rate of CAPA during ICU admission was investigated. The clinical factors associated with CAPA, including corticosteroid exposure, were analyzed. The impact of CAPA on the treatment outcomes and SARS-CoV-2 viral shedding were explored. RESULTS: A total of 72 ICU-admitted patients with COVID-19 were included in the analysis. The incidence rate of CAPA was 15.3% (11/72) in all patients and 23% (11/48) in the mechanically ventilated patients. The median time from ICU admission to CAPA diagnosis was 15 days. A lower fibrinogen level (adjusted odds ratio [aOR], 0.983; 95% confidence interval [CI], 0.967-0.999) was independently associated with CAPA. The patients with CAPA had a higher in-hospital mortality rate (55% vs. 13%, p = 0.001) and a longer SARS-CoV-2 viral shedding time (22 days vs. 16 days, p = 0.037) than those without CAPA. CONCLUSION: Lower serum fibrinogen levels was independently associated with CAPA among the ICU-admitted patients with COVID-19. The patients with CAPA had a higher in-hospital mortality rate and a longer SARS-CoV-2 viral shedding time than those without CAPA.
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COVID-19 , Aspergilosis Pulmonar , Humanos , SARS-CoV-2 , COVID-19/complicaciones , Esparcimiento de Virus , Mortalidad Hospitalaria , Estudios Retrospectivos , Unidades de Cuidados Intensivos , FibrinógenoRESUMEN
The PD-1/PD-L1 pathway is critical in T cell biology; however, the role of the PD-1/PD-L1 pathway in clinical characteristics and treatment outcomes in pulmonary tuberculosis (PTB) patients is unclear. We prospectively enrolled PTB, latent TB infection (LTBI), and non-TB, non-LTBI subjects. The expression of PD-1/PD-L1 on peripheral blood mononuclear cells (PBMCs) was measured and correlated with clinical characteristics and treatment outcomes in PTB patients. Immunohistochemistry and immunofluorescence were used to visualize PD-1/PD-L1-expressing cells in lung tissues from PTB patients and from murine with heat-killed MTB (HK-MTB) treatment. A total of 76 PTB, 40 LTBI, and 28 non-TB, non-LTBI subjects were enrolled. The expression of PD-1 on CD4+ T cells and PD-L1 on CD14+ monocytes was significantly higher in PTB cases than non-TB subjects. PTB patients with sputum smear/culture unconversion displayed higher PD-L1 expression on monocytes. PD-L1-expressing macrophages were identified in lung tissue from PTB patients, and co-localized with macrophages in murine lung tissues. Mycobacterium tuberculosis (MTB) whole cell lysate/EsxA stimulation of human and mouse macrophages demonstrated increased PD-L1 expression. In conclusion, increased expression of PD-L1 on monocytes in PTB patients correlated with higher bacterial burden and worse treatment outcomes. The findings suggest the involvement of the PD-1/PD-L1 pathway in MTB-related immune responses.
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Antituberculosos/farmacología , Antígeno B7-H1/metabolismo , Tuberculosis Latente/metabolismo , Leucocitos Mononucleares/metabolismo , Mycobacterium tuberculosis/patogenicidad , Receptor de Muerte Celular Programada 1/metabolismo , Tuberculosis Pulmonar/metabolismo , Regulación hacia Arriba , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antituberculosos/uso terapéutico , Estudios de Casos y Controles , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Humanos , Tuberculosis Latente/microbiología , Masculino , Ratones , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Células THP-1 , Resultado del Tratamiento , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Adulto JovenRESUMEN
INTRODUCTION: Even though alectinib is a potent second-generation ALK inhibitor with a favorable safety profile, alectinib-induced interstitial lung disease (ILD) could be fatal. There are case reports described successful alectinib rechallenge in mild ILD. However, the feasibility and safety of rechallenge in severe cases remains to be elucidated. CASE REPORT: A 76-year-old female was a case of stage IV lung adenocarcinoma harboring ALK rearrangement. Respiratory failure following severe ILD developed one month after alectinib administration. She received mechanical ventilation in intensive care uint. ILD subsided gradually after methylprednisolone pulse therapy and discontinuation of alectinib.Management and outcome: After the recovery from ILD, the patient attempted a re-escalation of alectinib from a lower dose under close clinical and radiological monitoring. No ILD happened even after 480 days of alectinib rechallenge. DISCUSSION: Given that the ALK inhibitors are the treatment of choice for advanced lung cancer patients with ALK rearrangement. Our report demonstrated the potential feasibility of alectinib re-use in cases of severe druginduced ILD.
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Adenocarcinoma del Pulmón/tratamiento farmacológico , Carbazoles/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Piperidinas/efectos adversos , Anciano , Carbazoles/administración & dosificación , Femenino , Humanos , Piperidinas/administración & dosificación , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
The PD-1/PD-L1 pathway plays a pivotal role in T cell activity and is involved in the pathophysiology of Mycobacterium tuberculosis (MTB) infection. DNA methylation is a mechanism that modulates PD-L1 expression in cancer cells. However, its effect on PD-L1 expression in macrophages after MTB infection remains unknown. We prospectively enrolled patients with active tuberculosis (TB) and non-TB subjects. The expression of PD-L1 and methylation-related genes in peripheral blood mononuclear cells (PBMCs) were investigated and their correlation with disease severity and treatment outcomes were examined. PD-L1 promoter methylation status was evaluated using bisulfite sequencing. Immunohistochemistry (IHC) and immunofluorescence (IF) staining were used to visualize PD-L1- and TET-1-expressing cells in lung tissues from patients with TB and in macrophage cell lines with MTB-related stimulation. In total, 80 patients with active TB and 40 non-TB subjects were enrolled in the analysis. Patients with active TB had significantly higher expression of PD-L1, DNMT3b, TET1, TET2, and lower expression of DNMT1, compared to that in the non-TB subjects. The expression of PD-L1 and TET-1 was significantly associated with 1-month smear and culture non-conversion. IHC and IF staining demonstrated the co-localization of PD-L1- and TET-1-expressing macrophages in patients with pulmonary TB and in human macrophage cell lines after MTB-related stimulation. DNMT inhibition and TET-1 knockdown in human macrophages increased and decreased PD-L1 expression, respectively. Overall, PD-L1 expression is increased in patients with active TB and is correlated with treatment outcomes. DNA methylation is involved in modulating PD-L1 expression in human macrophages.
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BACKGROUND: Despite vaccines' effectiveness in reducing COVID-19 infection rates and disease severity, their impact on critical patients presenting with acute respiratory failure is elusive. The aim of this study was to further investigate the influence of vaccination on mortality rates among severely ill COVID-19 patients experiencing acute respiratory failure. METHODS: This retrospective cohort study was carried out at a tertiary medical center in Taiwan. From April to September 2022, patients who tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through reverse transcription polymerase chain reaction (RT-PCR) and subsequently experienced acute respiratory failure were included in the study. Baseline characteristics, including vaccination history, along with information regarding critical illness and clinical outcomes, were gathered and compared between patients who received the vaccine and those who did not. RESULTS: A total of 215 patients with COVID-19 exhibiting acute respiratory failure, as confirmed via RTâPCR, were included in the analysis. Of this cohort, sixty-six (30.7%) patients died within 28 days. Neither administration of the vaccine nor achievement of primary series vaccination status had a significantly different effect on 28 day mortality, number of viral shedding events, acute respiratory distress syndrome (ARDS) incidence or other clinical outcomes. Patients who received the booster vaccine and completed the primary series showed a tendency of increased 28 days of ventilator-free status, though this difference was not statistically significant (p = 0.815). CONCLUSIONS: Vaccination status did not significantly influence mortality rates, the occurrence of ARDS, or the viral shedding duration in COVID-19 patients with acute respiratory failure.
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COVID-19 , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Vacunas , Humanos , COVID-19/prevención & control , COVID-19/complicaciones , Síndrome de Dificultad Respiratoria/etiología , Insuficiencia Respiratoria/etiología , Estudios Retrospectivos , SARS-CoV-2 , Resultado del Tratamiento , VacunaciónRESUMEN
BACKGROUND: Adverse reactions, especially nephrotoxicity, are great concerns of intravenous colistin treatment. The role of substitutive nebulized colistin in treating nosocomial pneumonia caused by carbapenem-resistant Gram-negative bacterial (CR-GNB) in critically ill patients remains unknown. METHODS: This retrospective study enrolled patients with nosocomial pneumonia caused by colistin-susceptible CRGNB in the intensive care unit (ICU) without intravenous colistin treatment. Patients were categorized based on whether substitutive nebulized colistin was used alongside other intravenous antibiotics. Clinical responses and mortality rates were compared between the two groups in the original and propensity score (PS)-matched cohorts. This study aimed to investigate the clinical effectiveness of substitutive nebulized colistin in treatment outcomes of nosocomial pneumonia caused by CR-GNB. The impact of dosing strategy of nebulized colistin was also explored. RESULTS: In total, 343 and 214 patients with and without substitutive nebulized colistin, respectively, were enrolled for analysis. In the PS-matched cohort, clinical failure rates on day 7 (22.6 vs. 42.6%, p = 0.001), day 14 (27.0 vs. 42.6%, p = 0.013), and day 28 (27.8 vs. 41.7%, p = 0.027) were significantly lower in patients with nebulized colistin. In multivariate analysis, nebulized colistin was an independent factor associated with lower day 14 clinical failure (Original cohort: adjusted odds ratio (aOR) 0.45, 95% confidence interval (CI) 0.30-0.67; PS-matched cohort: aOR 0.48, 95% CI 0.27-0.87). There were no differences in clinical failure rate and mortality rate between patients receiving high (> 6 MIU/day) and low (≤ 6 MIU/day) dose nebulized colistin in the PS-matched cohort. CONCLUSIONS: In ICU-admitted patients with nosocomial pneumonia caused by colistin-susceptible CRGNB, substitutive nebulized colistin was associated with better clinical outcomes.
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BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global outbreak disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cytomegalovirus (CMV) infection can occur in critical COVID-19 patients and is associated with adverse clinical outcomes. OBJECTIVE: The aim of this study was to explore the clinical characteristics and outcome of CMV infection in critical COVID-19 patients. DESIGN: This was a retrospective cohort study. METHODS: From May to September 2021, SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients with intensive care unit (ICU) admission were enrolled. CMV infection was confirmed by PCR. Baseline characteristics, critical illness data and clinical outcomes were recorded and analyzed. RESULTS: Seventy-two RT-PCR-confirmed COVID-19 patients with ICU admission were included during the study period and 48 (66.7%) patients required mechanical ventilation (MV). Overall, in-hospital mortality was 19.4%. Twenty-one (29.2%) patients developed CMV infection. Patients with CMV infection had a higher likelihood of diabetes, higher lactate dehydrogenase and lactate levels, and higher proportions of MV, anticoagulant, and steroid use. Patients with CMV infection were associated with longer duration of SARS-CoV-2 shedding, longer ICU and hospital stay, and fewer ventilator-free days. The independent risk factor for development of CMV infection was a higher accumulative steroid dose. CONCLUSION: CMV infection adversely impacted the outcomes of critical COVID-19 patients, resulting in longer ICU stays, longer mechanical ventilation uses and prolonged shedding of SARS-CoV-2.
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COVID-19 , Infecciones por Citomegalovirus , Humanos , COVID-19/diagnóstico , COVID-19/terapia , SARS-CoV-2 , Estudios Retrospectivos , Unidades de Cuidados Intensivos , Infecciones por Citomegalovirus/diagnóstico , EsteroidesRESUMEN
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a pandemic that has resulted in millions of deaths worldwide. Critically ill COVID-19 patients who require intubation and develop nosocomial pneumonia, commonly caused by gram-negative bacilli, have a higher mortality rate than those without nosocomial pneumonia. OBJECTIVES: The aim of this study is to compare the clinical characteristics and outcomes and associated risk factors of Alpha and Omicron SARS-CoV-2 variants in critically ill patients on mechanical ventilation (MV) with nosocomial pneumonia. DESIGN: This is a retrospective single-center cohort study. METHODS: This observational study was conducted at Taipei Veterans General Hospital, Taiwan from May 2021 to September 2022. Critically ill patients who had confirmed SARS-CoV-2 infection and intubated on a MV with bacterial pneumonia were enrolled. Demographic data, laboratory results, and treatment information were collected and analyzed. In addition, clinical outcomes among different SARS-CoV-2 variants were examined. RESULTS: This study included 94 critically ill COVID-19 patients who required intubation and intensive care unit (ICU) admission. The Alpha group had a longer duration of SARS-CoV-2 viral shedding, MV days, and ICU stay, while the Omicron group had older age, more comorbidities, higher APACHE II scores, and higher in-hospital mortality (47.0% versus 25.0%, p = 0.047). However, independent risk factors for in-hospital mortality included malignancy, lower serum albumin levels, and lack of Remdesivir treatment, except for the SARS-CoV-2 variant. CONCLUSION: Our study discovered a higher in-hospital mortality rate in severe COVID-19 patients with MV and secondary pneumonia infected with the Omicron variant compared to the Alpha variant; however, real independent risk factors for in-hospital mortality are malignancy, lower serum albumin level, and lack of Remdesivir treatment.
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COVID-19 , Infección Hospitalaria , Neumonía Asociada a la Atención Médica , Neoplasias , Humanos , COVID-19/terapia , SARS-CoV-2 , Respiración Artificial , Enfermedad Crítica/terapia , Estudios Retrospectivos , Estudios de Cohortes , Unidades de Cuidados Intensivos , Albúmina SéricaRESUMEN
OBJECTIVES: This study explored the clinical outcomes and association of prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding in patients with severe coronavirus disease 2019 (COVID-19) infection who developed nosocomial pneumonia. METHODS: This was a retrospective study conducted in a medical center in Taiwan. From May to September 2021, patients from four intensive care units were enrolled after SARS-CoV-2 was confirmed through quantitative polymerase chain reaction and all cases were compatible with the definitions of severe COVID-19 infection. Baseline characteristics, disease severity, clinical outcomes, and times of viral shedding were recorded. RESULTS: A total of 72 patients were diagnosed as having severe COVID-19 infection and 30 developed nosocomial pneumonia, comprising hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). The patients with severe COVID-19 infection and concomitant HAP/VAP had longer intensive care unit (ICU) stays and fewer ventilator-free days at Day 28. An independent risk factor for nosocomial pneumonia was a greater SOFA score at admission. Furthermore, the patients with severe COVID-19 infection who developed HAP/VAP had a significantly longer duration of SARS-CoV-2 shedding (19.50 days vs. 15.00 days, p = 0.006). CONCLUSIONS: Patients with severe COVID-19 infection who developed nosocomial pneumonia had longer SARS-CoV-2 shedding days, more complications, and worse outcomes.