PaCO2 Association with Outcomes of Patients with Traumatic Brain Injury at High Altitude: A Prospective Single-Center Cohort Study.

BACKGROUND: Partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes. METHODS: This is a prospective single-center cohort of consecutive patients with TBI admitted to a trauma center located at 2600 m above sea level. An unfavorable outcome was defined as a Glasgow Outcome Scale-Extended (GOSE) score < 4 at the 6-month follow-up. RESULTS: We had a total of 81 patients with complete data, 80% (65/81) were men, and the median (interquartile range) age was 36 (25-50) years. Median Glasgow Coma Scale (GCS) score on admission was 9 (6-14); 49% (40/81) of patients had severe TBI (GCS 3-8), 32% (26/81) had moderate TBI (GCS 12-9), and 18% (15/81) had mild TBI (GCS 13-15). The median (interquartile range) Abbreviated Injury Score of the head (AISh) was 3 (2-4). The frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), the median GOSE was 4 (2-5), and the median 6-month mortality rate was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, (median age 49 [30-72] vs. 29 [22-41] years, P < 0.01), had lower admission GCS scores (6 [4-8] vs. 13 [8-15], P < 0.01), had higher AISh scores (4 [4-4] vs. 3 [2-4], P < 0.01), had higher Acute Physiology and Chronic Health disease Classification System II scores (17 [15-23] vs. 10 [6-14], P < 0.01), had higher Charlson scores (0 [0-2] vs. 0 [0-0], P < 0.01), and had higher PaCO2 levels (mean 35 ± 8 vs. 32 ± 6 mm Hg, P < 0.01). In a multivariate analysis, age (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.1-1.30, P < 0.01), AISh (OR 4.7, 95% CI 1.55-21.0, P < 0.05), and PaCO2 levels (OR 1.23, 95% CI 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4, 95% CI 1.61-28.5, P = 0.017) and PaCO2 levels (OR 1.36, 95% CI 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome. CONCLUSIONS: Higher PaCO2 levels are associated with an unfavorable outcome in ventilated patients with TBI. These results underscore the importance of PaCO2 levels in patients with TBI and whether it should be adjusted for populations living at higher altitudes.

PaCO2 Association with Traumatic Brain Injury Patients Outcomes at High Altitude: A Prospective Single-Center Cohort Study.

Background: partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes. Methods: This is a prospective single-center cohort of consecutive TBI patients admitted to a trauma center located at 2600 meter above sea level. An unfavorable outcome was defined as the Glasgow Outcome Scale-Extended (GOSE) < 4 at 6-month follow-up. Results: 81 patients with complete data, 80% (65/81) were men, and median (IQR) age was 36 (25-50) years). Median Glasgow Coma Scale (GCS) on admission was 9 (6-14), 49% (40/81) were severe (GCS: 3-8), 32% (26/81) moderate (GCS 12 - 9), and 18% (15/81) mild (GCS 13-15) TBI. The median (IQR) Abbreviated Injury Score of the Head (AISh) was 3 (2-4). Frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), median GOSE was 4 (2-5), and 6-month mortality was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, median [49 (30-72) vs. 29 (22-41), P < 0.01], had lower admission GCS [6 (4-8) vs. 13 (8-15), P < 0.01], higher AIS head [4 (4-4) vs. 3(2-4), p < 0.01], higher APACHE II score [17(15-23) vs 10 (6-14), < 0.01), higher Charlson score [0(0-2) vs. 0 (0-0), P < 0.01] and higher PaCO2 (mmHg), mean ± SD, 39 ± 9 vs. 32 ± 6, P < 0.01. In a multivariate analysis, age (OR 1.14 95% CI 1.1-1.30, P < 0.01), AISh (OR 4.7 95% CI 1.55-21.0, P < 0.05), and PaCO2 (OR 1.23 95% CI: 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4 95% CI: 1.61-28.5, P = 0.017) and PaCO2 (OR 1.36 95% CI: 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome. Conclusion: Higher PaCO2 levels are associated with an unfavorable outcome in ventilated TBI patients. These results underscore the importance of PaCO2 level in TBI patients and whether it should be adjusted for populations living at higher altitudes.

Vagus Nerve Stimulation in Ischemic Stroke.

PURPOSE OF REVIEW: Vagus nerve stimulation (VNS) has emerged as a potential therapeutic approach for neurological and psychiatric disorders. In recent years, there has been increasing interest in VNS for treating ischemic stroke. This review discusses the evidence supporting VNS as a treatment option for ischemic stroke and elucidates its underlying mechanisms. RECENT FINDINGS: Preclinical studies investigating VNS in stroke models have shown reduced infarct volumes and improved neurological deficits. Additionally, VNS has been found to reduce reperfusion injury. VNS may promote neuroprotection by reducing inflammation, enhancing cerebral blood flow, and modulating the release of neurotransmitters. Additionally, VNS may stimulate neuroplasticity, thereby facilitating post-stroke recovery. The Food and Drug Administration has approved invasive VNS (iVNS) combined with rehabilitation for ischemic stroke patients with moderate to severe upper limb deficits. However, iVNS is not feasible in acute stroke due to its time-sensitive nature. Non-invasive VNS (nVNS) may be an alternative approach for treating ischemic stroke. While the evidence from preclinical studies and clinical trials of nVNS is promising, the mechanisms through which VNS exerts its beneficial effects on ischemic stroke are still being elucidated. Therefore, further research is needed to better understand the efficacy and underlying mechanisms of nVNS in ischemic stroke. Moreover, large-scale randomized clinical trials are necessary to determine the optimal nVNS protocols, assess its long-term effects on stroke recovery and outcomes, and identify the potential benefits of combining nVNS with other rehabilitation strategies.

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Hospital Course, Confounders, and Medications.

The convergence of an interdisciplinary team of neurocritical care specialists to organize the Curing Coma Campaign is the first effort of its kind to coordinate national and international research efforts aimed at a deeper understanding of disorders of consciousness (DoC). This process of understanding includes translational research from bench to bedside, descriptions of systems of care delivery, diagnosis, treatment, rehabilitation, and ethical frameworks. The description and measurement of varying confounding factors related to hospital care was thought to be critical in furthering meaningful research in patients with DoC. Interdisciplinary hospital care is inherently varied across geographical areas as well as community and academic medical centers. Access to monitoring technologies, specialist consultation (medical, nursing, pharmacy, respiratory, and rehabilitation), staffing resources, specialty intensive and acute care units, specialty medications and specific surgical, diagnostic and interventional procedures, and imaging is variable, and the impact on patient outcome in terms of DoC is largely unknown. The heterogeneity of causes in DoC is the source of some expected variability in care and treatment of patients, which necessitated the development of a common nomenclature and set of data elements for meaningful measurement across studies. Guideline adherence in hemorrhagic stroke and severe traumatic brain injury may also be variable due to moderate or low levels of evidence for many recommendations. This article outlines the process of the development of common data elements for hospital course, confounders, and medications to streamline definitions and variables to collect for clinical studies of DoC.

Risk factors and outcomes of lower respiratory tract infections after traumatic brain injury: a retrospective observational study.

Background: Traumatic brain injury (TBI) is a public health problem with a high burden in terms of disability and death. Infections are a common complication, with respiratory infections being the most frequent. Most available studies have addressed the impact of ventilator-associated pneumonia (VAP) after TBI; therefore, we aim to characterize the hospital impact of a broader entity, lower respiratory tract infections (LRTIs). Methods: This observational, retrospective, single-center cohort study describes the clinical features and risk factors associated with LRTIs in patients with TBI admitted to an intensive care unit (ICU). We used bivariate and multivariate logistic regressions to identify the risk factors associated with developing LRTI and determine its impact on hospital mortality. Results: We included 291 patients, of whom 77% (225/291) were men. The median (IQR) age was 38 years (28-52 years). The most common cause of injury was road traffic accidents 72% (210/291), followed by falls 18% (52/291) and assault at 3% (9/291). The median (IQR) Glasgow Coma Scale (GCS) score on admission was 9 (6-14), and 47% (136/291) were classified as severe TBI, 13% (37/291) as moderate TBI, and 40% (114/291) as mild TBI. The median (IQR) injury severity score (ISS) was 24 (16-30). Nearly 48% (141/291) of patients presented at least one infection during hospitalization, and from those, 77% (109/141) were classified as LRTIs, which included tracheitis 55% (61/109), ventilator-associated pneumonia (VAP) 34% (37/109), and hospital-acquired pneumoniae (HAP) 19% (21/109). After multivariable analysis, the following variables were significantly associated with LRTIs: age (OR 1.1, 95% CI 1.01-1.2), severe TBI (OR 2.7, 95% CI 1.1-6.9), AIS thorax (OR 1.4, 95 CI 1.1-1.8), and mechanical ventilation on admission (OR 3.7, 95% CI 1.1-13.5). At the same time, hospital mortality did not differ between groups (LRTI 18.6% vs. No LRTI 20.1%, p = 0.7), and ICU and hospital length of stay (LOS) were longer in the LRTI group (median [IQR] 12 [9-17] vs. 5 [3-9], p < 0.01) and (median [IQR] 21 [13-33] vs. 10 [5-18], p = 0.01), respectively. Time on the ventilator was longer for those with LRTIs. Conclusion: The most common site/location of infection in patients with TBI admitted to ICU is respiratory. Age, severe TBI, thoracic trauma, and mechanical ventilation were identified as potential risk factors. LRTI was associated with prolonged ICU, hospital stay, and more days on a ventilator, but not with mortality.

The Respiratory Rate-Oxygenation Index predicts failure of post-extubation high-flow nasal cannula therapy in intensive care unit patients: a retrospective cohort study. / Índice de Oxigenação Respiratória prevê falha de pós-extubação com cânula nasal de alto fluxo em pacientes de unidade de terapia intensiva: estudo de coorte retrospectivo.

OBJECTIVE: To investigate the applicability of the Respiratory Rate-Oxygenation Index to identify the risk of high-flow nasal cannula failure in post-extubation pneumonia patients. METHODS: This was a 2-year retrospective observational study conducted in a reference hospital in Bogotá, Colombia. All patients in whom post-extubation high-flow nasal cannula therapy was used as a bridge to extubation were included in the study. The Respiratory Rate-Oxygenation Index was calculated to assess the risk of post-extubation high-flow nasal cannula failure. RESULTS: A total of 162 patients were included in the study. Of these, 23.5% developed high-flow nasal cannula failure. The Respiratory Rate-Oxygenation Index was significantly lower in patients who had high-flow nasal cannula failure [median (IQR): 10.0 (7.7 - 14.4) versus 12.6 (10.1 - 15.6); p = 0.006]. Respiratory Rate-Oxygenation Index > 4.88 showed a crude OR of 0.23 (95%CI 0.17 - 0.30) and an adjusted OR of 0.89 (95%CI 0.81 - 0.98) stratified by severity and comorbidity. After logistic regression analysis, the Respiratory Rate-Oxygenation Index had an adjusted OR of 0.90 (95%CI 0.82 - 0.98; p = 0.026). The area under the Receiver Operating Characteristic curve for extubation failure was 0.64 (95%CI 0.53 - 0.75; p = 0.06). The Respiratory Rate-Oxygenation Index did not show differences between patients who survived and those who died during the intensive care unit stay. CONCLUSION: The Respiratory Rate-Oxygenation Index is an accessible tool to identify patients at risk of failing high-flow nasal cannula post-extubation treatment. Prospective studies are needed to broaden the utility in this scenario.

OBJETIVO: Investigar a aplicabilidade do Índice de Oxigenação Respiratória para identificar o risco de falha de cânula nasal de alto fluxo em pacientes com pneumonia. MÉTODOS: Este estudo retrospectivo observacional de 2 anos foi realizado em um hospital de referência em Bogotá, na Colômbia. Incluíram-se no estudo todos os pacientes em que foi utilizada cânula nasal de alto fluxo pós-extubação como terapia-ponte para a extubação. O Índice de Oxigenação Respiratória foi calculado para avaliar o risco de falha pós-extubação de cânula nasal de alto fluxo. RESULTADOS: Incluíram-se no estudo 162 pacientes. Destes, 23,5% apresentaram falha de cânula nasal de alto fluxo. O Índice de Oxigenação Respiratória foi significativamente menor em pacientes que tiveram falha de cânula nasal de alto fluxo. A mediana (IQ 25 - 75%) foi de 10,0 (7,7 - 14,4) versus 12,6 (10,1 - 15,6), com p = 0,006. O Índice de Oxigenação Respiratória > 4,88 apresentou razão de chances bruta de 0,23 (IC95% 0,17 - 0,30) e RC ajustada de 0,89 (IC95% 0,81 - 0,98) estratificada por gravidade e comorbidade. Após a análise de regressão logística, o Índice de Oxigenação Respiratória apresentou razão de chances ajustada de 0,90 (IC95% 0,82 - 0,98; p = 0,026). A área sob a curva Receiver Operating Characteristic para falha de extubação foi de 0,64 (IC95% 0,53 - 0,75; p = 0,06). O Índice de Oxigenação Respiratória não apresentou diferenças entre pacientes que sobreviveram e que morreram durante internação na unidade de terapia intensiva. CONCLUSÃO: O Índice de Oxigenação Respiratória é uma ferramenta acessível para identificar pacientes em risco de falha no tratamento pós-extubação com cânulas nasais de alto fluxo. Estudos prospectivos são necessários para ampliar a utilidade nesse cenário.

Negative predictive value of procalcitonin to rule out bacterial respiratory co-infection in critical covid-19 patients.

BACKGROUND: Procalcitonin (PCT) and C-Reactive Protein (CRP) are useful biomarkers to differentiate bacterial from viral or fungal infections, although the association between them and co-infection or mortality in COVID-19 remains unclear. METHODS: The study represents a retrospective cohort study of patients admitted for COVID-19 pneumonia to 84 ICUs from ten countries between (March 2020-January 2021). Primary outcome was to determine whether PCT or CRP at admission could predict community-acquired bacterial respiratory co-infection (BC) and its added clinical value by determining the best discriminating cut-off values. Secondary outcome was to investigate its association with mortality. To evaluate the main outcome, a binary logistic regression was performed. The area under the curve evaluated diagnostic performance for BC prediction. RESULTS: 4635 patients were included, 7.6% fulfilled BC diagnosis. PCT (0.25[IQR 0.1-0.7] versus 0.20[IQR 0.1-0.5]ng/mL, p<0.001) and CRP (14.8[IQR 8.2-23.8] versus 13.3 [7-21.7]mg/dL, p=0.01) were higher in BC group. Neither PCT nor CRP were independently associated with BC and both had a poor ability to predict BC (AUC for PCT 0.56, for CRP 0.54). Baseline values of PCT<0.3ng/mL, could be helpful to rule out BC (negative predictive value 91.1%) and PCT≥0.50ng/mL was associated with ICU mortality (OR 1.5,p<0.001). CONCLUSIONS: These biomarkers at ICU admission led to a poor ability to predict BC among patients with COVID-19 pneumonia. Baseline values of PCT<0.3ng/mL may be useful to rule out BC, providing clinicians a valuable tool to guide antibiotic stewardship and allowing the unjustified overuse of antibiotics observed during the pandemic, additionally PCT≥0.50ng/mL might predict worsening outcomes.

Índice de Oxigenação Respiratória prevê falha de pós-extubação com cânula nasal de alto fluxo em pacientes de unidade de terapia intensiva: estudo de coorte retrospectivo / The Respiratory Rate-Oxygenation Index predicts failure of post-extubation high-flow nasal cannula therapy in intensive care unit patients: a retrospective cohort study

RESUMO Objetivo: Investigar a aplicabilidade do Índice de Oxigenação Respiratória para identificar o risco de falha de cânula nasal de alto fluxo em pacientes com pneumonia. Métodos: Este estudo retrospectivo observacional de 2 anos foi realizado em um hospital de referência em Bogotá, na Colômbia. Incluíram-se no estudo todos os pacientes em que foi utilizada cânula nasal de alto fluxo pós-extubação como terapia-ponte para a extubação. O Índice de Oxigenação Respiratória foi calculado para avaliar o risco de falha pós-extubação de cânula nasal de alto fluxo. Resultados: Incluíram-se no estudo 162 pacientes. Destes, 23,5% apresentaram falha de cânula nasal de alto fluxo. O Índice de Oxigenação Respiratória foi significativamente menor em pacientes que tiveram falha de cânula nasal de alto fluxo. A mediana (IQ 25 - 75%) foi de 10,0 (7,7 - 14,4) versus 12,6 (10,1 - 15,6), com p = 0,006. O Índice de Oxigenação Respiratória > 4,88 apresentou razão de chances bruta de 0,23 (IC95% 0,17 - 0,30) e RC ajustada de 0,89 (IC95% 0,81 - 0,98) estratificada por gravidade e comorbidade. Após a análise de regressão logística, o Índice de Oxigenação Respiratória apresentou razão de chances ajustada de 0,90 (IC95% 0,82 - 0,98; p = 0,026). A área sob a curva Receiver Operating Characteristic para falha de extubação foi de 0,64 (IC95% 0,53 - 0,75; p = 0,06). O Índice de Oxigenação Respiratória não apresentou diferenças entre pacientes que sobreviveram e que morreram durante internação na unidade de terapia intensiva. Conclusão: O Índice de Oxigenação Respiratória é uma ferramenta acessível para identificar pacientes em risco de falha no tratamento pós-extubação com cânulas nasais de alto fluxo. Estudos prospectivos são necessários para ampliar a utilidade nesse cenário.

ABSTRACT Objective: To investigate the applicability of the Respiratory Rate-Oxygenation Index to identify the risk of high-flow nasal cannula failure in post-extubation pneumonia patients. Methods: This was a 2-year retrospective observational study conducted in a reference hospital in Bogotá, Colombia. All patients in whom post-extubation high-flow nasal cannula therapy was used as a bridge to extubation were included in the study. The Respiratory Rate-Oxygenation Index was calculated to assess the risk of post-extubation high-flow nasal cannula failure. Results: A total of 162 patients were included in the study. Of these, 23.5% developed high-flow nasal cannula failure. The Respiratory Rate-Oxygenation Index was significantly lower in patients who had high-flow nasal cannula failure [median (IQR): 10.0 (7.7 - 14.4) versus 12.6 (10.1 - 15.6); p = 0.006]. Respiratory Rate-Oxygenation Index > 4.88 showed a crude OR of 0.23 (95%CI 0.17 - 0.30) and an adjusted OR of 0.89 (95%CI 0.81 - 0.98) stratified by severity and comorbidity. After logistic regression analysis, the Respiratory Rate-Oxygenation Index had an adjusted OR of 0.90 (95%CI 0.82 - 0.98; p = 0.026). The area under the Receiver Operating Characteristic curve for extubation failure was 0.64 (95%CI 0.53 - 0.75; p = 0.06). The Respiratory Rate-Oxygenation Index did not show differences between patients who survived and those who died during the intensive care unit stay. Conclusion: The Respiratory Rate-Oxygenation Index is an accessible tool to identify patients at risk of failing high-flow nasal cannula post-extubation treatment. Prospective studies are needed to broaden the utility in this scenario.

Clinical characteristics, systemic complications, and in-hospital outcomes for patients with COVID-19 in Latin America. LIVEN-Covid-19 study: A prospective, multicenter, multinational, cohort study.

PURPOSE: The COVID-19 pandemic has spread worldwide, and almost 396 million people have been infected around the globe. Latin American countries have been deeply affected, and there is a lack of data in this regard. This study aims to identify the clinical characteristics, in-hospital outcomes, and factors associated with ICU admission due to COVID-19. Furthermore, to describe the functional status of patients at hospital discharge after the acute episode of COVID-19. MATERIAL AND METHODS: This was a prospective, multicenter, multinational observational cohort study of subjects admitted to 22 hospitals within Latin America. Data were collected prospectively. Descriptive statistics were used to characterize patients, and multivariate regression was carried out to identify factors associated with severe COVID-19. RESULTS: A total of 3008 patients were included in the study. A total of 64.3% of patients had severe COVID-19 and were admitted to the ICU. Patients admitted to the ICU had a higher mean (SD) 4C score (10 [3] vs. 7 [3)], p<0.001). The risk factors independently associated with progression to ICU admission were age, shortness of breath, and obesity. In-hospital mortality was 24.1%, whereas the ICU mortality rate was 35.1%. Most patients had equal self-care ability at discharge 43.8%; however, ICU patients had worse self-care ability at hospital discharge (25.7% [497/1934] vs. 3.7% [40/1074], p<0.001). CONCLUSIONS: This study confirms that patients with SARS CoV-2 in the Latin American population had a lower mortality rate than previously reported. Systemic complications are frequent in patients admitted to the ICU due to COVID-19, as previously described in high-income countries.

Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats.

Introduction: Spontaneously hypertensive stroke-prone rats (SHRSP) are used to model clinically relevant aspects of human cerebral small vessel disease (CSVD). To decipher and understand the underlying disease dynamics, assessment of the temporal progression of CSVD histopathological and neuroimaging correlates is essential. Materials and Methods: Eighty age-matched male SHRSP and control Wistar Kyoto rats (WKY) were randomly divided into four groups that were aged until 7, 16, 24 and 32 weeks. Sensorimotor testing was performed weekly. Brain MRI was acquired at each study time point followed by histological analyses of the brain. Results: Compared to WKY controls, the SHRSP showed significantly higher prevalence of small subcortical hyperintensities on T2w imaging that progressed in size and frequency with aging. Volumetric analysis revealed smaller intracranial and white matter volumes on brain MRI in SHRSP compared to age-matched WKY. Diffusion tensor imaging (DTI) showed significantly higher mean diffusivity in the corpus callosum and external capsule in WKY compared to SHRSP. The SHRSP displayed signs of motor restlessness compared to WKY represented by hyperactivity in sensorimotor testing at the beginning of the experiment which decreased with age. Distinct pathological hallmarks of CSVD, such as enlarged perivascular spaces, microbleeds/red blood cell extravasation, hemosiderin deposits, and lipohyalinosis/vascular wall thickening progressively accumulated with age in SHRSP. Conclusions: Four stages of CSVD severity in SHRSP are described at the study time points. In addition, we find that quantitative analyses of brain MRI enable identification of in vivo markers of CSVD that can serve as endpoints for interventional testing in therapeutic studies.

Effect of High-Flow Oxygen Therapy vs Conventional Oxygen Therapy on Invasive Mechanical Ventilation and Clinical Recovery in Patients With Severe COVID-19: A Randomized Clinical Trial.

IMPORTANCE: The effect of high-flow oxygen therapy vs conventional oxygen therapy has not been established in the setting of severe COVID-19. OBJECTIVE: To determine the effect of high-flow oxygen therapy through a nasal cannula compared with conventional oxygen therapy on need for endotracheal intubation and clinical recovery in severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label clinical trial conducted in emergency and intensive care units in 3 hospitals in Colombia. A total of 220 adults with respiratory distress and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 200 due to COVID-19 were randomized from August 2020 to January 2021, with last follow-up on February 10, 2021. INTERVENTIONS: Patients were randomly assigned to receive high-flow oxygen through a nasal cannula (n = 109) or conventional oxygen therapy (n = 111). MAIN OUTCOMES AND MEASURES: The co-primary outcomes were need for intubation and time to clinical recovery until day 28 as assessed by a 7-category ordinal scale (range, 1-7, with higher scores indicating a worse condition). Effects of treatments were calculated with a Cox proportional hazards model adjusted for hypoxemia severity, age, and comorbidities. RESULTS: Among 220 randomized patients, 199 were included in the analysis (median age, 60 years; n = 65 women [32.7%]). Intubation occurred in 34 (34.3%) randomized to high-flow oxygen therapy and in 51 (51.0%) randomized to conventional oxygen therapy (hazard ratio, 0.62; 95% CI, 0.39-0.96; P = .03). The median time to clinical recovery within 28 days was 11 (IQR, 9-14) days in patients randomized to high-flow oxygen therapy vs 14 (IQR, 11-19) days in those randomized to conventional oxygen therapy (hazard ratio, 1.39; 95% CI, 1.00-1.92; P = .047). Suspected bacterial pneumonia occurred in 13 patients (13.1%) randomized to high-flow oxygen and in 17 (17.0%) of those randomized to conventional oxygen therapy, while bacteremia was detected in 7 (7.1%) vs 11 (11.0%), respectively. CONCLUSIONS AND RELEVANCE: Among patients with severe COVID-19, use of high-flow oxygen through a nasal cannula significantly decreased need for mechanical ventilation support and time to clinical recovery compared with conventional low-flow oxygen therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04609462.

Burden of invasive pneumococcal disease (IPD) over a 10-year period in Bogotá, Colombia.

BACKGROUND: Invasive pneumococcal disease (IPD) is the leading cause of infectious death worldwide. This study aimed to describe the epidemiology of IPD and the impact of pneumococcal conjugate vaccine-10 (PCV-10) over a 10-year period in Bogotá, Colombia. METHODS: This was a laboratory-based surveillance study of Streptococcus pneumoniae isolated from patients with IPD from 82 hospitals over 10 years in Bogotá, Colombia. Data were compared between two periods: 2007-2011 (before the introduction of PCV-10) and 2012-2017 (after the introduction of PCV-10). RESULTS: In total, 1670 patients with IPD were included in the study between 2007 and 2017. Between 2007 and 2011, the most common serotypes were 14, 1, 6B, 6A and 3. Between 2012 and 2017, the most common serotypes were 19A, 3, 14 and 1. A decrease in the incidence of IPD, particularly in children aged 0-4 years, was noted after the introduction of PCV-10. Importantly, this reduction in incidence was not observed in patients aged ≥50 years. CONCLUSIONS: The IPD burden in Bogotá remained stable between 2007 and 2017. The incidence of IPD decreased in children but not in older adults. The introduction of PCV-10 led to a change in the most prevalent serotypes to serotypes that are not included in PCV-10.

The Use of GMP-Produced Bone Marrow-Derived Stem Cells in Combination with Extracorporeal Membrane Oxygenation in ARDS: An Animal Model.

Acute respiratory distress syndrome (ARDS) is the result of a wide variety of disorders, which can be associated with different clinical disorders or systemic diseases directly affecting the lungs. Currently, the only existing therapy is limited to supportive care. In a 6 hour pilot study, we analyzed the use of the combination of both stem cell and extracorporeal membrane oxygenation (ECMO) strategies to prevent or treat severe lung injury. A total of 11 sheep were used. Five sheep received Escherichia coli endotoxin as a control group (group 1). Three sheep that received E. coli endotoxin were treated with veno-venous ECMO support in group 2. In group 3, 3 sheep received a dose of clinical grade good manufacturing practice (GMP)-produced MultiPotent Adult Progenitor cells (MAPC) intratracheally after the end of the infusion of E. coli endotoxin, followed by ECMO support. The respiratory parameters by means of blood gas results, measurements of lung injury, inflammatory responses, and integrity of the alveolar capillary barrier after the infusion of these cells were analyzed. Our data suggest that the combination of ECMO and stem cell therapy showed better histopathologic changes with less inflammation. We believe that the combination of stem cells with the ECMO treatment may be useful in future studies investigating the diagnosis, treatment, and prevention of ARDS.

Human adult bone marrow-derived stem cells decrease severity of lipopolysaccharide-induced acute respiratory distress syndrome in sheep.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill subjects, sepsis and severe bacterial pneumonia being its most common causes. The only interventions that have proven beneficial are protective ventilation strategies and fluid conservation approaches. New therapies are needed to address this common clinical problem. Others and we have previously shown the beneficial effect of infusion of exogenous adult stem cells in different pre-clinical models of ARDS. METHODS: In the present study endotoxin was infused intravenously into 14 sheep from which 6 received different doses of adult stem cells by intrabronchial delivery to evaluate the effect of stem cell therapy. RESULTS: After administration of endotoxin, there was a rapid decline in oxygenation to hypoxemic values, indicative of severe-to-moderate ARDS. None of the animals treated with saline solution recovered to normal baseline values during the 6 hours that the animals were followed. In contrast, sheep treated with a dose of 40 million adult stem cells returned their levels of oxygen in their blood to baseline two hours after the cells were infused. Similarly, improvements in carbon dioxide (CO2) clearance, pulmonary vascular pressures and inflammation were observed and confirmed by histology and by the decrease in lung edema. CONCLUSIONS: We concluded that instillation of adult non-hematopoietic stem cells can diminish the impact of endotoxin and accelerate recovery of oxygenation, CO2 removal and inflammation in the ovine model, making the use of adult stem cells a real alternative for future therapies for ARDS.

Mesenchymal stem cells: a promising therapy for the acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a pulmonary syndrome with growing prevalence and high mortality and morbidity that increase with age. There is no current therapy able to restore pulmonary function in ARDS patients. Preclinical models of ARDS have demonstrated that intratracheal or systemic administration of mesenchymal stem cells (MSCs) protects the lung against injury. The mechanisms responsible for the protective effects are multiple, including the secretion of multiple paracrine factors capable of modulating the immune response and restoring epithelial and endothelial integrity. Recent studies have demonstrated that MSCs can also control oxidative stress, transfer functional mitochondria to the damaged cells, and control bacterial infection by secretion of antibacterial peptides. These characteristics make MSCs promising candidates for ARDS therapy.