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BACKGROUND: When patients with a tracheostomy tube reach a stage in their care at which decannulation appears to be possible, it is common practice to cap the tracheostomy tube for 24 hours to see whether they can breathe on their own. Whether this approach to establishing patient readiness for decannulation leads to better outcomes than one based on the frequency of airway suctioning is unclear. METHODS: In five intensive care units (ICUs), we enrolled conscious, critically ill adults who had a tracheostomy tube; patients were eligible after weaning from mechanical ventilation. In this unblinded trial, patients were randomly assigned either to undergo a 24-hour capping trial plus intermittent high-flow oxygen therapy (control group) or to receive continuous high-flow oxygen therapy with frequency of suctioning being the indicator of readiness for decannulation (intervention group). The primary outcome was the time to decannulation, compared by means of the log-rank test. Secondary outcomes included decannulation failure, weaning failure, respiratory infections, sepsis, multiorgan failure, durations of stay in the ICU and hospital, and deaths in the ICU and hospital. RESULTS: The trial included 330 patients; the mean (±SD) age of the patients was 58.3±15.1 years, and 68.2% of the patients were men. A total of 161 patients were assigned to the control group and 169 to the intervention group. The time to decannulation was shorter in the intervention group than in the control group (median, 6 days [interquartile range, 5 to 7] vs. 13 days [interquartile range, 11 to 14]; absolute difference, 7 days [95% confidence interval, 5 to 9]). The incidence of pneumonia and tracheobronchitis was lower, and the duration of stay in the hospital shorter, in the intervention group than in the control group. Other secondary outcomes were similar in the two groups. CONCLUSIONS: Basing the decision to decannulate on suctioning frequency plus continuous high-flow oxygen therapy rather than on 24-hour capping trials plus intermittent high-flow oxygen therapy reduced the time to decannulation, with no evidence of a between-group difference in the incidence of decannulation failure. (REDECAP ClinicalTrials.gov number, NCT02512744.).
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Remoción de Dispositivos , Terapia por Inhalación de Oxígeno , Succión , Traqueostomía , Enfermedad Crítica , Femenino , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno/métodos , Factores de Tiempo , Desconexión del VentiladorRESUMEN
BACKGROUND: There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19. METHODS: We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels. RESULTS: We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10-8) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15×10-10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95×10-8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48×10-4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06×10-5). CONCLUSIONS: We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).
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Sistema del Grupo Sanguíneo ABO/genética , Betacoronavirus , Cromosomas Humanos Par 3/genética , Infecciones por Coronavirus/genética , Predisposición Genética a la Enfermedad , Neumonía Viral/genética , Polimorfismo de Nucleótido Simple , Insuficiencia Respiratoria/genética , Anciano , COVID-19 , Estudios de Casos y Controles , Cromosomas Humanos Par 9/genética , Infecciones por Coronavirus/complicaciones , Femenino , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Italia , Masculino , Persona de Mediana Edad , Familia de Multigenes , Pandemias , Neumonía Viral/complicaciones , Insuficiencia Respiratoria/etiología , SARS-CoV-2 , EspañaRESUMEN
OBJECTIVES: Ceftazidime/avibactam and cefiderocol are two of the latest antibiotics with activity against a wide variety of Gram-negatives, including carbapenem-resistant Enterobacterales. We sought to describe the phenotypic and genotypic characteristics of ceftazidime/avibactam- and cefiderocol-resistant KPC-Klebsiella pneumoniae (KPC-Kp) detected during an outbreak in 2020 in the medical ICU of our hospital. METHODS: We collected 11 KPC-Kp isolates (6 clinical; 5 surveillance samples) resistant to ceftazidime/avibactam and cefiderocol from four ICU patients (November 2020 to January 2021), without prior exposure to these agents. All patients had a decontamination regimen as part of the standard ICU infection prevention protocol. Additionally, one ceftazidime/avibactam- and cefiderocol-resistant KPC-Kp (June 2019) was retrospectively recovered. Antibiotic susceptibility was determined by broth microdilution. ß-Lactamases were characterized and confirmed. WGS was also performed. RESULTS: All KPC-Kp isolates (ceftazidime/avibactam MIC â≥16/4 mg/L; cefiderocol MIC ≥4 mg/L) were KPCâ+âCTX-M-15 producers and belonged to the ST307 high-risk-clone (ST307-HRC). KPC-62 (L168Q) was detected in all isolates involved in the 2020 outbreak, contained in January 2021. KPC-31 (D179Y) was identified in the KPC-Kp from 2019. Cloning experiments demonstrated that both blaKPC-62 and blaKPC-31 were responsible for ceftazidime/avibactam resistance (MIC >16 mg/L) and an increased cefiderocol MIC. Additionally, mutations in OmpA and EnvZ/OmpR porin proteins (in KPC-62-Kp) and in PBP2 (in KPC-31-Kp) were found and may be involved in cefiderocol resistance. CONCLUSIONS: The emergence of resistance to both ceftazidime/avibactam and cefiderocol in KPC-Kp-HRCs, together with the diversification of novel KPC enzymes displaying different antibiotic resistance phenotypes, is an epidemiological and clinical risk.
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Ceftazidima , Infecciones por Klebsiella , Humanos , Ceftazidima/farmacología , Ceftazidima/uso terapéutico , Klebsiella pneumoniae , España/epidemiología , Estudios Retrospectivos , Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/tratamiento farmacológico , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Hospitales Universitarios , CefiderocolRESUMEN
Diffuse alveolar damage and thrombi are the most common lung histopathological lesions reported in patients with severe COVID-19. Although some studies have suggested increased pulmonary angiogenesis, the presence of vascular proliferation in COVID-19 lungs has not been well characterised. Glomeruloid-like microscopic foci and/or coalescent vascular proliferations measuring up to 2 cm were present in the lung of 14 out of 16 autopsied patients. These lesions expressed CD31, CD34 and vascular endothelial cadherin. Platelet-derived growth factor receptor-ß immunohistochemistry and dual immunostaining for CD34/smooth muscle actin demonstrated the presence of pericytes. These vascular alterations may contribute to the severe and refractory hypoxaemia that is common in patients with severe COVID-19.
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COVID-19 , Autopsia , Proliferación Celular , Humanos , Pulmón , SARS-CoV-2RESUMEN
Background: This multicentre, observational, retrospective chart review study assessed ceftaroline fosamil treatment patterns and outcomes in adults hospitalized with community-acquired pneumonia (CAP) in usual care settings. Methods: Anonymized patient data were extracted from hospital records of adults with CAP who received ≥4 consecutive IV ceftaroline fosamil doses at sites in Brazil, Colombia, France, Greece, Italy, Russia and Spain. Results: The dataset included 185 patients (58.9% male; mean age 62.2â years), of whom 128 (69.2%) had severe CAP defined by CURB-65, PSI/PORT score or physician judgement. Streptococcus pneumoniae (nâ=â44; 23.8%) and Staphylococcus aureus [MSSA (nâ=â15) and MRSA (nâ=â14)] were the most frequently identified pathogens. Clinical response occurred in 151 (81.6%) patients overall, and in 104 (81.3%) severe CAP patients. Response within ≤4 and >4â days occurred in 79 (42.7%) and 62 (33.5%) patients (unknown, nâ=â10), respectively. Twenty (10.8%) patients required readmission within 30â days. Thirty-day all-cause mortality rates were 9.7% (nâ=â18) overall and 10.2% (nâ=â13) in severe CAP. In sensitivity analysis using ICU admission as a more objective marker of severe CAP (nâ=â75), clinical response and 30â day mortality occurred in 57 (76.0%) and 10 (13.3%) patients, respectively. Overall, clinical response to ceftaroline fosamil was associated with >60% shorter length of ICU stay (3.6 versus 9.2â days), and >30% lower hospital costs ($8449 versus $12â559) versus non-responders. Conclusions: Ceftaroline fosamil was effective in treating adults with CAP, including severe CAP, in Europe and Latin America. Clinical response to ceftaroline fosamil was associated with reductions in healthcare resource use compared with non-responders.
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Serratia marcescens is an opportunistic pathogen historically associated with sudden outbreaks in intensive care units (ICUs) and the spread of carbapenem-resistant genes. However, the ecology of S. marcescens populations in the hospital ecosystem remains largely unknown. We combined epidemiological information of 1,432 Serratia spp. isolates collected from sinks of a large ICU that underwent demographic and operational changes (2019-2021) and 99 non-redundant outbreak/non-outbreak isolates from the same hospital (2003-2019) with 165 genomic data. These genomes were grouped into clades (1-4) and subclades (A and B) associated with distinct species: Serratia nematodiphila (1A), S. marcescens (1B), Serratia bockelmannii (2A), Serratia ureilytica (2B), S. marcescens/Serratia nevei (3), and S. nevei (4A and 4B). They may be classified into an S. marcescens complex (SMC) due to the similarity between/within subclades (average nucleotide identity >95%-98%), with clades 3 and 4 predominating in our study and publicly available databases. Chromosomal AmpC ß-lactamase with unusual basal-like expression and prodigiosin-lacking species contrasted classical features of Serratia. We found persistent and coexisting clones in sinks of subclades 4A (ST92 and ST490) and 4B (ST424), clonally related to outbreak isolates carrying blaVIM-1 or blaOXA-48 on prevalent IncL/pB77-CPsm plasmids from our hospital since 2017. The distribution of SMC populations in ICU sinks and patients reflects how Serratia species acquire, maintain, and enable plasmid evolution in both "source" (permanent, sinks) and "sink" (transient, patients) hospital patches. The results contribute to understanding how water sinks serve as reservoirs of Enterobacterales clones and plasmids that enable the persistence of carbapenemase genes in healthcare settings, potentially leading to outbreaks and/or hospital-acquired infections.IMPORTANCEThe "hospital environment," including sinks and surfaces, is increasingly recognized as a reservoir for bacterial species, clones, and plasmids of high epidemiological concern. Available studies on Serratia epidemiology have focused mainly on outbreaks of multidrug-resistant species, overlooking local longitudinal analyses necessary for understanding the dynamics of opportunistic pathogens and antibiotic-resistant genes within the hospital setting. This long-term genomic comparative analysis of Serratia isolated from the ICU environment with isolates causing nosocomial infections and/or outbreaks within the same hospital revealed the coexistence and persistence of Serratia populations in water reservoirs. Moreover, predominant sink strains may acquire highly conserved and widely distributed plasmids carrying carbapenemase genes, such as the prevalent IncL-pB77-CPsm (pOXA48), persisting in ICU sinks for years. The work highlights the relevance of ICU environmental reservoirs in the endemicity of certain opportunistic pathogens and resistance mechanisms mainly confined to hospitals.
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Infección Hospitalaria , Unidades de Cuidados Intensivos , Infecciones por Serratia , Serratia marcescens , Serratia marcescens/genética , Serratia marcescens/aislamiento & purificación , Serratia marcescens/clasificación , Infecciones por Serratia/epidemiología , Infecciones por Serratia/microbiología , Humanos , Infección Hospitalaria/microbiología , Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Genoma Bacteriano , Hospitales , Filogenia , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , beta-Lactamasas/genética , Pruebas de Sensibilidad MicrobianaRESUMEN
INTRODUCTION: It has recently been proposed that B lymphocytes are involved in sepsis pathogenesis. The goal of this study is to investigate potential abnormalities in a subset distribution and activation of circulating B lymphocytes in patients with septic shock. METHODS: This observational prospective study was conducted in a medical-surgical ICU. All patients with septic shock were eligible for inclusion. B-cell phenotypes (CD19+CD69+, CD19+CD23+, CD19+CD5+, CD19+CD80, CD19+CD86+, CD19+CD40 and CD19+CD95+) were assessed by quantitative flow cytometry upon admission to the ICU and 3, 7, 14 and 28 d later. RESULTS: Fifty-two patients were included. Thirty-six healthy volunteers matched for age and sex were used as controls. The patients had lymphopenia that was maintained during 28 d of follow-up. In patients with septic shock who died, the percentage of CD19+CD23+ was lower during the 7 d of follow-up than it was in survival patients. Moreover, the percentage of CD80+ and CD95+ expression on B cells was higher in patients who died than in survivors. Receiver operating characteristic curve analysis showed that a CD19+CD23+ value of 64.6% at ICU admission enabled discrimination between survivors and nonsurvivors with a sensitivity of 90.9% and a specificity of 80.0% (P=0.0001). CONCLUSIONS: Patients with septic shock who survive and those who don't have different patterns of abnormalities in circulating B lymphocytes. At ICU admission, a low percentage of CD23+ and a high of CD80+ and CD95+ on B cells were associated with increased mortality of patients with septic shock. Moreover, a drop in circulating B cells persisted during 28 d of ICU follow-up.
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Linfocitos B/metabolismo , Choque Séptico/sangre , Choque Séptico/diagnóstico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Choque Séptico/mortalidad , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
BACKGROUND: There are few data regarding the process of deciding which elderly patients are refused to ICU admission, their characteristics, and outcome. METHODS: Prospective longitudinal observational cohort study. We included all consecutive patients older than 75 years, who were evaluated for admission to but were refused to treatment in ICU, during 18 months, with 12-month followup. We collected demographic data, ICU admission/refusal reasons, previous functional and cognitive status, comorbidity, severity of illness, and hospital and 12-month mortality. RESULTS: 338 elderly patients were evaluated for ICU admission and 88 were refused to ICU (26%). Patients refused because they were "too ill to benefit" had more comorbidity and worse functional and mental situation than those admitted to ICU; there were no differences in illness severity. Hospital mortality rate of the whole study cohort was 36.3%, higher in patients "too ill to benefit" (55.6% versus 35.8%, P < 0.01), which also have higher 1-year mortality (73.7% versus 42.5%, P < 0.01). High comorbidity, low functional status, unavailable ICU beds, and age were associated with refusal decision on multivariate analysis. CONCLUSIONS: Prior functional status and comorbidity, not only the age or severity of illness, can help us more to make the right decision of admitting or refusing to ICU patients older than 75 years.
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Unidades de Cuidados Intensivos , Admisión del Paciente , Negativa al Tratamiento , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Comorbilidad , Femenino , Mortalidad Hospitalaria , Humanos , Estudios Longitudinales , Masculino , Readmisión del Paciente , Estudios Prospectivos , España/epidemiologíaRESUMEN
Recently, several studies about the role of natural killer (NK) cells in sepsis have been highlighted. In an earlier study, we characterized the abnormalities of circulating lymphocytes in 52 patients with septic shock during the first 28 days in the intensive care unit. Our results confirm and expand some previous reports. We found that patients who did not survive exhibited less NK cell (CD3-CD56âº) depletion than survivors and that these NK cells expressed CD69⺠and CD57âº. These data demonstrate that NK cells are key participants in septic shock because patients who survived have more depletion and expressed less early activation and differentiation.
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Mortalidad Hospitalaria , Unidades de Cuidados Intensivos/estadística & datos numéricos , Células Asesinas Naturales/inmunología , Sepsis/sangre , Sepsis/mortalidad , Choque Séptico/sangre , Choque Séptico/patología , Subgrupos de Linfocitos T/patología , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Prompt evaluation and treatment of acute coronary syndrome has demonstrated to reduce mortality. Although several biomarkers have been studied for risk stratification and prognostic purposes, none is recommended to guide treatment based on its prognostic value. Copeptin and hepatocyte growth factor have been associated with poor outcome in patients with acute myocardial infarction. The aim of this study is to evaluate the early prognostic value of measurements of copeptin and hepatocyte growth factor for hospital mortality risk and 1-year-follow-up mortality, in patients with acute myocardial infarction. In our retrospective observational study, we measured hepatocyte growth factor and copeptin in blood samples collected at hospital arrival in patients with acute myocardial infarction; and follow-up them until 1-year. RESULTS: 84 patients with were included in the study, mainly male (65%) with a median age of 70.3 ± 13.56 years. Hospital mortality was 11.9%. Plasma levels of copeptin at hospital arrival were statistically significant higher in patients who died during hospital admission (145.60 pmol/L [52.21-588.50] vs. 24.79 pmol/L [10.90-84.82], p 0.01). However, we found no statistically significant association between plasma levels of hepatocyte growth factor and hospital mortality (381.05 pg/ml [189.95-736.65] vs. 355.24 pg/ml [175.55-521.76], p 0.73). 1-year follow-up mortality was 21.4%. Plasma levels of copeptin at hospital arrival were higher in those patients who died in the following year (112.28 pmol/L [25.10-418.27] vs. 23.82 pmol/L [10.96-77.30], p 0.02). In the case of HGF, we also find no association between hepatocyte growth factor plasma levels and 1 -year follow-up mortality (350.00 pg/ml [175.05-555.08] vs. 345.53 pg/ml [183.68-561.15], p 0.68). CONCLUSIONS: In patients with acute myocardial infarction measurement of copeptin at hospital arrival could be a useful tool to assess the prognosis of these patients, since their elevation is associated with a higher hospital mortality and higher 1-year follow-up mortality. We have not found this association in the case of hepatocyte growth factor measurement.
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BACKGROUND: High-flow nasal cannula (HFNC) was shown to be non-inferior to noninvasive ventilation (NIV) for preventing reintubation in a general population of high-risk patients. However, some subgroups of high-risk patients might benefit more from NIV. We aimed to determine whether the presence of many risk factors or overweight (body mass index (BMI) ≥ 25 kg/m2) patients could have different response to any preventive therapy, NIV or HFNC in terms of reduced reintubation rate. METHODS: Not pre-specified post hoc analysis of a multicentre, randomized, controlled, non-inferiority trial comparing NFNC and NIV to prevent reintubation in patients at risk for reintubation. The original study included patients with at least 1 risk factor for reintubation. RESULTS: Among 604 included in the original study, 148 had a BMI ≥ 25 kg/m2. When adjusting for potential covariates, patients with ≥ 4 risk factors (208 patients) presented a higher risk for reintubation (OR 3.4 [95%CI 2.16-5.35]). Patients with ≥ 4 risk factors presented lower reintubation rates when treated with preventive NIV (23.9% vs 45.7%; P = 0.001). The multivariate analysis of overweight patients, adjusted for covariates, did not present a higher risk for reintubation (OR 1.37 [95%CI 0.82-2.29]). However, those overweight patients presented an increased risk for reintubation when treated with preventive HFNC (OR 2.47 [95%CI 1.18-5.15]). CONCLUSIONS: Patients with ≥ 4 risk factors for reintubation may benefit more from preventive NIV. Based on this result, HFNC may not be the optimal preventive therapy in overweight patients. Specific trials are needed to confirm these results.
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The development of lung fibrosis is a major concern in patients recovered from severe COVID-19 pneumonia. This study aimed to document the evolution of diffuse alveolar damage (DAD) to the fibrosing pattern and define the transcriptional programs involved. Morphological, immunohistochemical and transcriptional analysis were performed in lung samples obtained from autopsy of 33 severe COVID-19 patients (median illness duration: 36 days). Normal lung and idiopathic pulmonary fibrosis (IPF) were used for comparison. Twenty-seven patients with DAD and disease evolution of more than 2 weeks had fibrosis. Pathways and genes related with collagen biosynthesis and extracellular matrix (ECM) biosynthesis and degradation, myofibroblastic differentiation and epithelial to mesenchymal transition (EMT) were overexpressed in COVID-19. This pattern had similarities with that observed in IPF. By immunohistochemistry, pathological fibroblasts (pFBs), with CTHRC1 and SPARC expression, increased in areas of proliferative DAD and decreased in areas of mature fibrosis. Immunohistochemical analysis demonstrated constitutive expression of cadherin-11 in normal epithelial cells and a similar pattern of cadherin and catenin expression in epithelial cells from both normal and COVID-19 samples. Transcriptomic analysis revealed downregulation of the Hippo pathway, concordant with the observation of YAP overexpression in hyperplastic alveolar epithelial cells. Progression to fibrosis in severe COVID-19 is associated with overexpression of fibrogenic pathways and increased in CTHRC1- and SPARC-positive pFBs. Whereas the Hippo pathway seemed to be implicated in the response to epithelial cell damage, EMT was not a major process implicated in COVID-19 mediated lung fibrosis.
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Severe cases of Coronavirus Disease 2019 (COVID-19) can present with multiple neurological symptoms. The available neuropathological studies have described different lesions; the most frequent was the presence of neuroinflammation and vascular-related lesions. The objective of this study was to report the neuropathological studies performed in a medical institution, with abundant long intensive care unit stays, and their associated clinical manifestations. This is a retrospective monocentric case series study based on the neuropathological reports of 13 autopsies with a wide range of illness duration (13-108 days). A neuroinflammatory score was calculated based on the quantification of CD8- and CD68-positive cells in representative areas of the central nervous system. This score was correlated afterwards with illness duration and parameters related to systemic inflammation. Widespread microglial and cytotoxic T-cell activation was found in all patients. There was no correlation between the neuroinflammatory score and the duration of the illness; nor with parameters of systemic inflammation such as the peak of IL-6 or the HScore (a parameter of systemic macrophage activation syndrome). Two patients had global hypoxic ischaemic damage and five patients had subacute infarcts. One patient had many more brain vascular microthrombi compared to the others and multiple subacute pituitary infarcts. SARS-CoV-2 RNA was not detected with qRT-PCR. The proportion of brain lesions in severe COVID-19 patients could be related to illness duration. In our series, with abundant long hospitalisation stays, neuroinflammation was present in all patients and was more prominent between day 34 and day 45 after onset of symptoms. Clinical correlation showed that two patients with the highest neuroinflammatory scores had severe encephalopathies that were not attributable to any other cause. The second most frequent lesions were related to vascular pathology.
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COVID-19 , Enfermedades del Sistema Nervioso , COVID-19/complicaciones , Humanos , Infarto , Inflamación , Interleucina-6 , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/patología , Estudios Retrospectivos , SARS-CoV-2RESUMEN
The exact role of viral replication in patients with severe COVID-19 has not been extensively studied, and it has only been possible to demonstrate the presence of replicative virus for more than 3 months in a few cases using different techniques. Our objective was to study the presence of RNA SARS-CoV-2 in autopsy samples of patients who died from COVID-19 long after the onset of symptoms. Secondary superimposed pulmonary infections present in these patients were also studied. We present an autopsy series of 27 COVID-19 patients with long disease duration, where pulmonary and extrapulmonary samples were obtained. In addition to histopathological analysis, viral genomic RNA (gRNA) and viral subgenomic RNA (sgRNA) were detected using RT-PCR and in situ hybridization, and viral protein was detected using immunohistochemistry. This series includes 26 adults with a median duration of 39 days from onset of symptoms to death (ranging 9-108 days), 92% of them subjected to immunomodulatory therapy, and an infant patient. We detected gRNA in the lung of all but one patient, including those with longer disease duration. SgRNA was detected in 11 out of 17 patients (64.7%) with illness duration up to 6 weeks and in 3 out of 9 patients (33.3%) with more than 6 weeks of disease progression. Viral protein was detected using immunohistochemistry and viral mRNA was detected using in situ hybridization in 3 out of 4 adult patients with illness duration of <2 weeks, but in none of the 23 adult patients with an illness duration of >2 weeks. A remarkable result was the detection of viral protein, gRNA and sgRNA in the lung cells of the pediatric patient after 95 days of illness. Additional pulmonary infections included: 9 acute bronchopneumonia, 2 aspergillosis, 2 cytomegalovirus, and 1 BK virus infection. These results suggest that in severe COVID-19, SARS-CoV-2 could persist for longer periods than expected, especially in immunocompromised populations, contributing to the persistence of chronic lung lesions. Additional infections contribute to the fatal course of the disease.
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BACKGROUND: During the first wave of the COVID-19 pandemic, shortages of ventilators and ICU beds overwhelmed health care systems. Whether early tracheostomy reduces the duration of mechanical ventilation and ICU stay is controversial. RESEARCH QUESTION: Can failure-free day outcomes focused on ICU resources help to decide the optimal timing of tracheostomy in overburdened health care systems during viral epidemics? STUDY DESIGN AND METHODS: This retrospective cohort study included consecutive patients with COVID-19 pneumonia who had undergone tracheostomy in 15 Spanish ICUs during the surge, when ICU occupancy modified clinician criteria to perform tracheostomy in Patients with COVID-19. We compared ventilator-free days at 28 and 60 days and ICU- and hospital bed-free days at 28 and 60 days in propensity score-matched cohorts who underwent tracheostomy at different timings (≤ 7 days, 8-10 days, and 11-14 days after intubation). RESULTS: Of 1,939 patients admitted with COVID-19 pneumonia, 682 (35.2%) underwent tracheostomy, 382 (56%) within 14 days. Earlier tracheostomy was associated with more ventilator-free days at 28 days (≤ 7 days vs > 7 days [116 patients included in the analysis]: median, 9 days [interquartile range (IQR), 0-15 days] vs 3 days [IQR, 0-7 days]; difference between groups, 4.5 days; 95% CI, 2.3-6.7 days; 8-10 days vs > 10 days [222 patients analyzed]: 6 days [IQR, 0-10 days] vs 0 days [IQR, 0-6 days]; difference, 3.1 days; 95% CI, 1.7-4.5 days; 11-14 days vs > 14 days [318 patients analyzed]: 4 days [IQR, 0-9 days] vs 0 days [IQR, 0-2 days]; difference, 3 days; 95% CI, 2.1-3.9 days). Except hospital bed-free days at 28 days, all other end points were better with early tracheostomy. INTERPRETATION: Optimal timing of tracheostomy may improve patient outcomes and may alleviate ICU capacity strain during the COVID-19 pandemic without increasing mortality. Tracheostomy within the first work on a ventilator in particular may improve ICU availability.
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COVID-19/terapia , Unidades de Cuidados Intensivos , Neumonía Viral/terapia , Respiración Artificial , Traqueostomía , Anciano , Ocupación de Camas/estadística & datos numéricos , COVID-19/epidemiología , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/virología , Puntaje de Propensión , Estudios Retrospectivos , España/epidemiologíaRESUMEN
BACKGROUND: Mortality in patients with septic shock remains unacceptably high and the attempts to antagonize certain proinflammatory cytokines based on the results of animal model studies have failed to improve survival rates. The objective of this article is to examine the pro-/anti-inflammatory cytokine balance in patients with septic shock and its connection with mortality. METHODS: Serum levels of proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin 1ß [IL-1ß], interferonγ [IFN-γ], and IL-6) and soluble cytokine antagonists (soluble TNF receptor I [sTNF-RI], sTNF-RII, and IL-1Ra) were determined on admission to the intensive care unit (ICU) and 3, 7, 14, and 28 days later in 52 patients with septic shock and in 36 healthy controls. Specific sandwich enzyme-linked immunosorbent assay (ELISA) was used for all determinations. RESULTS: Serum levels of most of the pro- and anti-inflammatory molecules examined (TNF-α, IL-6, sTNF-RI, sTNF-RII, and IL-1 receptor agonist [IL-1Ra]) were significantly elevated on admission and during the 28-day observation period in patients when compared to controls. Notably, the anti-inflammatory mediators sTNF-RI, sTNF-RII, and IL-1Ra were better predictors of mortality. Receiver-operating characteristic (ROC) analysis revealed that sTNF-RI or sTNF-RII concentrations over 2767 or 4619 pg/mL, respectively, determined a high risk of death (sensitivity: 100%-100%, specificity: 57.1%-71.4%, area under the curve [AUC] 0.759-0.841, respectively), whereas IL-1Ra concentrations below 7033 pg/mL determined a high probability of survival (sensitivity: 60%, specificity: 100%, AUC 0.724). In addition, IFN-γ levels were significantly higher in survivors than in controls during the initial 2 weeks of observation. CONCLUSIONS: Our data show that serum cytokine disturbance patterns have prognostic significance in patients with septic shock admitted to the ICU. The pattern, defined by an early response to continuously elevated anti-inflammatory cytokine serum levels, is associated with an enhanced risk of a fatal outcome for patients.
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Cuidados Críticos , Choque Séptico/sangre , Choque Séptico/mortalidad , Anciano , Femenino , Humanos , Interferón gamma/sangre , Proteína Antagonista del Receptor de Interleucina 1/sangre , Interleucina-1beta/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Receptores Tipo II del Factor de Necrosis Tumoral/sangre , Sensibilidad y Especificidad , Choque Séptico/patología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a cytosolic protein that is released into the bloodstream when the myocardium is injured. The aim was to determine the diagnostic and prognostic value of H-FABP in patients with suspected acute myocardial infarction (AMI) within the first 3-6 hours after the onset of chest pain. METHODS AND RESULTS: A consecutive series of 165 patients with chest pain lasting less than 6 hours were enrolled in a forward observational design in the emergency department.The diagnostic validity of H-FABP was evaluated according to sensitivity, specificity, and predictive values, likelihood ratios, ROC curves, and multivariate logistic regression analyses. The prognostic value of H-FABP at 6 months was checked using survival curves and the multivariate Cox proportional hazards model. The sensitivity of H-FABP was 81% (95% CI: 69.2-92.9). Its area under the ROC curve: 0.729 (95% CI: 0.63-0.83) and negative likelihood ratio (0.38; 95% CI: 0.22-0.65) were significantly better than both troponin (cTnI) and CK-MB, whereas its specificity, 53% (95% CI: 41.1-64.8), was lower than that of the other markers. Increased H-FABP added diagnostic information as it demonstrated independent association with AMI by logistic regression analysis. Increased H-FABP and cTnI were both strong and independent predictors of outcome in the 6-month follow-up (hazard ratio: 2.18; 95% CI: 1.07-4.42; and 2.34; 95% CI: 0.98-5.59, respectively). CONCLUSIONS: H-FABP is, within 6 hours and also within 3 hours, more sensitive than the other markers in the early diagnosis of AMI and it is an independent prediction factor of events within 6 months.
Asunto(s)
Proteínas de Unión a Ácidos Grasos/sangre , Infarto del Miocardio/diagnóstico , Anciano , Anciano de 80 o más Años , Proteína 3 de Unión a Ácidos Grasos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Curva ROC , Sensibilidad y Especificidad , Troponina I/sangreRESUMEN
Nosocomial pneumonia is one of the most frequent infections in critical patients. It is primarily associated with mechanical ventilation leading to severe illness, high mortality, and prolonged hospitalization. The risk of mortality has increased over time due to the rise in multidrug-resistant (MDR) bacterial infections, which represent a global public health threat. Respiratory tract microbiome (RTM) research is growing, and recent studies suggest that a healthy RTM positively stimulates the immune system and, like the gut microbiome, can protect against pathogen infection through colonization resistance (CR). Physiological conditions of critical patients and interventions as antibiotics administration and mechanical ventilation dramatically alter the RTM, leading to dysbiosis. The dysbiosis of the RTM of ICU patients favors the colonization by opportunistic and resistant pathogens that can be part of the microbiota or acquired from the hospital environments (biotic or built ones). Despite recent evidence demonstrating the significance of RTM in nosocomial infections, most of the host-RTM interactions remain unknown. In this context, we present our perspective regarding research in RTM altered ecology in the clinical environment, particularly as a risk for acquisition of nosocomial pneumonia. We also reflect on the gaps in the field and suggest future research directions. Moreover, expected microbiome-based interventions together with the tools to study the RTM highlighting the "omics" approaches are discussed.
RESUMEN
The role of SARS-CoV-2 as a direct cause in the cardiac lesions in patients with severe COVID-19 remains to be established. Our objective is to report the pathological findings in cardiac samples of 30 patients who died after a prolonged hospital stay due to Sars-Cov-2 infection. We performed macroscopic, histological and immunohistochemical analysis of the hearts of 30 patients; and detected Sars-Cov-2 RNA by RT-PCR in the cardiac tissue samples. The median age of our cohort was 69.5 years and 76.6% were male. The median time between symptoms onset and death was 36.5 days. The main comorbidities were arterial hypertension (13 patients, 43.3%), dyslipidemia (11 patients, 36.7%), cardiovascular conditions (8 patients, 26.7%), and obesity (8 patients, 26.7%). Cardiovascular conditions included ischemic cardiopathy in 4 patients (13.3%), hypertrophic cardiomyopathy in 2 patients (6.7%) and valve replacement and chronic heart failure in one patient each (3.3%). At autopsy, the most frequent histopathological findings were coronary artery atherosclerosis (8 patients, 26.7%), left ventricular hypertrophy (4 patients, 13.3%), chronic epicardial inflammation (3 patients, 10%) and adipose metaplasia (2 patients, 6.7%). Two patients showed focal myocarditis, one due to invasive aspergillosis. One additional patient showed senile amyloidosis. Sars-Cov-2 RNA was detected in the heart of only one out of 30 patients, who had the shortest disease evolution of the series (9 days). However, no relevant cardiac histological alterations were identified. In present series, cardiac pathology was only modest in most patients with severe COVID-19. At present, the contribution of a direct effect of SARS-CoV-2 on cardiac lesions remains to be established.