Frailty in severe COVID-19 survivors after ICU admission. A prospective and multicenter study in Mexico.

OBJECTIVE: To analyze the presence of frailty in survivors of severe COVID-19 admitted in the Intensive Care Unit (ICU) and followed six months after discharge. DESIGN: An observational, prospective and multicenter, nation-wide study. SETTING: Eight adult ICU across eight academic acute care hospitals in Mexico. PATIENTS: All consecutive adult COVID-19 patients admitted in the ICU with acute respiratory failure between March 8, 2020 to February 28, 2021 were included. Frailty was defined according to the FRAIL scale, and was obtained at ICU admission and 6-month after hospital discharge. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: The primary endpoint was the frailty status 6-months after discharge. A regression model was used to evaluate the predictors during ICU stay associated with frailty. RESULTS: 196 ICU survivors were evaluated for basal frailty at ICU admission and were included in this analysis. After 6-months from discharge, 164 patients were evaluated for frailty: 40 patients (20.4%) were classified as non-frail, 67 patients (34.2%) as pre-frail and 57 patients (29.1%) as frail. After adjustment, the need of invasive mechanical ventilation was the only factor independently associated with frailty at 6 month follow-up (Odds Ratio [OR] 3.70, 95% confidence interval 1.40-9.81, P = .008). CONCLUSIONS: Deterioration of frailty was reported frequently among ICU survivors with severe COVID-19 at 6-months. The need of invasive mechanical ventilation in ICU survivors was the only predictor independently associated with frailty.

Características clínicas de mujeres con cáncer de mama triple negativo en una institución de cuarto nivel de Barranquilla / Clinical characteristics of women with triple-negative breast cancer in a fourth-level institution in Barranquilla

Introducción: El cáncer de mama triple negativo (TNBC) se caracteriza por la ausencia de receptores hormonales estrogénicos y progesterona; así como, del receptor 2 del factor de crecimiento epidérmico humano (HER2). Los TNBC se asocian con altas tasas de recurrencia, metástasis rápidas, supervivencia deficiente y mayor mortalidad en comparación con otros subtipos histológicos de cáncer de mama. El objetivo de este estudio fue establecer la prevalencia del TNBC; Así también, las características clínicas, en pacientes atendidas en un centro oncológico de referencia en Bogotá. Metodología: Estudio retrospectivo descriptivo transversal observacional, donde se evaluó la frecuencia del cáncer de mama subtipo triple negativo, Asimismo, las variables clínicas. En mujeres atendidas en la Organización Clínica Bonnadona Prevenir S.A.S. en Barranquilla, Colombia en el periodo 2021-2022. Resultados: Se estudiaron 350 pacientes, de los cuales 61 pacientes (17.4%) presentaban el inmunofenotipo triple negativo. La edad promedio fue de 54.5 años, 74% eran multíparas, 85% brindaron lactancia materna, 70% eran postmenopáusicas y el estadio clínico más frecuente fue el IIIB. Conclusión: En el presente estudio el 57.35% de la población exhibió un estadio clínico avanzado en el momento del diagnóstico; así mismo, las características clínicas son congruentes con los reportes en la literatura.

Introduction: Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen, progesterone hormone receptors, and human epidermal growth factor receptor 2 (HER2). TNBC is associated with an increased recurrence rate, distant metastasis, poor survival, and higher mortality than other pathological breast cancer subtypes. The objective of this study was to establish the prevalence of TNBC, likewise, with the clinical characteristics, in patients treated in a reference cancer center in Bogotá. Methodology: A retrospective descriptive cross-sectional observational study, where the frequency of triple negative subtype breast cancer was evaluated, as well as clinical variables and gynecologic and obstetric history, women treated at the Organización Clínica Bonnadona Prevenir S.A.S. in Barranquilla, Colombia in the period 2021-2022. Results: 350 patients were studied, of which 61 (17.4%) presented the triple-negative immunophenotype. The average age was 54, 74% were multiparous, 85% were breastfed, 70% were menopausal, and the most frequent clinical stage was IIIB. Conclusion: In this study, 57.35% of the population exhibited an advanced clinical stage at the time of diagnosis; Likewise, the clinical characteristics are consistent with the reports in the literature.

Gender Bias When Using Artificial Intelligence to Assess Anorexia Nervosa on Social Media: Data-Driven Study.

BACKGROUND: Social media sites are becoming an increasingly important source of information about mental health disorders. Among them, eating disorders are complex psychological problems that involve unhealthy eating habits. In particular, there is evidence showing that signs and symptoms of anorexia nervosa can be traced in social media platforms. Knowing that input data biases tend to be amplified by artificial intelligence algorithms and, in particular, machine learning, these methods should be revised to mitigate biased discrimination in such important domains. OBJECTIVE: The main goal of this study was to detect and analyze the performance disparities across genders in algorithms trained for the detection of anorexia nervosa on social media posts. We used a collection of automated predictors trained on a data set in Spanish containing cases of 177 users that showed signs of anorexia (471,262 tweets) and 326 control cases (910,967 tweets). METHODS: We first inspected the predictive performance differences between the algorithms for male and female users. Once biases were detected, we applied a feature-level bias characterization to evaluate the source of such biases and performed a comparative analysis of such features and those that are relevant for clinicians. Finally, we showcased different bias mitigation strategies to develop fairer automated classifiers, particularly for risk assessment in sensitive domains. RESULTS: Our results revealed concerning predictive performance differences, with substantially higher false negative rates (FNRs) for female samples (FNR=0.082) compared with male samples (FNR=0.005). The findings show that biological processes and suicide risk factors were relevant for classifying positive male cases, whereas age, emotions, and personal concerns were more relevant for female cases. We also proposed techniques for bias mitigation, and we could see that, even though disparities can be mitigated, they cannot be eliminated. CONCLUSIONS: We concluded that more attention should be paid to the assessment of biases in automated methods dedicated to the detection of mental health issues. This is particularly relevant before the deployment of systems that are thought to assist clinicians, especially considering that the outputs of such systems can have an impact on the diagnosis of people at risk.

Endoscopic ultrasound-guided resolution of right hydronephrosis secondary to local compression by an inflammatory pancreatic mass.

We present the case of 67 years-old man with unremarkable medical history. He was admitted to our department for abdominal pain compatible with choledocholithiasis associated with acute cholecystitis. ERCP was performed but direct papillary canulation attempts failed by means of conventional sphincterotome. So, pre- cut papillotomy was successfully attempted getting free access to distal choledochus and retrieving a small lithiasis. Unfortunately, the patient developed severe post-ERCP acute pancreatitis.

Association between pre-bronchoscopy time of illness and post-bronchoscopy discharge time in pediatric patients with foreign body aspiration: retrospective cohort study in a Peruvian referral center, 2014-2019. / Asociación entre el tiempo de enfermedad previo a broncoscopia y tiempo de alta posbroncoscopia en pacientes pediátricos con aspiración de cuerpo extraño: estudio de cohorte retrospectivo en un centro de referencia peruano, 2014-2019.

OBJECTIVE.: To determine the association between pre-bronchoscopy time of illness and post-bronchoscopy discharge time in pediatric patients with foreign body aspiration. MATERIALS AND METHODS.: Retrospective cohort study. Medical records were studied and reviewed at the Pediatric Emergency Hospital of Lima, Peru. We reviewed 324 medical records, and selected 183 because they had the diagnosis of foreign body aspiration and complete data. Fisher's exact test and Mann Whitney U test were used for the bivariate analysis, while Poisson regression was used to calculate the Relative Risk (RR) and its 95% confidence interval (CI). RESULTS.: We included 183 patients, of whom 65.6% were men with a mean age of 2.4 years. The most frequent location of the foreign body was the right bronchial tree and most of them were made of organic material. The majority (72.7%) of patients were discharged before 24 hours. We found an association between the time of illness prior to bronchoscopy and post-bronchoscopy discharge time (RR: 2.94, 95%CI: 1.72 - 5.01). CONCLUSIONS.: The time of illness prior to bronchoscopy and the length of hospital stay after removal of the foreign body were significantly associated when adjusted for age, sex, type of foreign body and mouth sweep maneuver as a rescue measure. Our findings are relevant because they highlight the importance of early care, timely diagnosis and early management of pediatric patients.

OBJETIVOS.: Determinar la asociación entre el tiempo de enfermedad previo a broncoscopia y el tiempo de alta posbroncoscopia en pacientes pediátricos con aspiración de cuerpo extraño. MATERIALES Y MÉTODOS.: Estudio de cohorte retrospectivo. El estudio y la revisión de historias clínicas se realizó en el Hospital de Emergencias Pediátricas de Lima, Perú. Se revisaron 324 historias clínicas, de las cuales, 183 historias fueron seleccionadas por contar con diagnóstico de cuerpo extraño en vías aéreas y estar adecuadamente llenadas. Para el análisis bivariado se utilizó la prueba exacta de Fisher y U de Mann Whitney, mientras que para el cálculo del riesgo relativo (RR) y su respectivo intervalo de confianza (IC) al 95% se utilizó regresión de Poisson. RESULTADOS.: Se incluyeron 183 pacientes, de los cuales, el 65,6% fueron hombres con una media de 2,4 años. La localización más frecuente fue el árbol bronquial derecho y cuerpo extraño de material orgánico. La mayoría (72,7%) de pacientes tuvieron un alta temprana antes de las 24 horas. Se encontró una asociación entre el tiempo de enfermedad previo a la broncoscopia y el tiempo alta posbroncoscopia (RR: 2,94, IC 95%: 1,72-5,01). CONCLUSIONES.: Existe una asociación estadísticamente significativa entre el tiempo de enfermedad previo a la broncoscopia y el tiempo de estancia hospitalaria posextracción del cuerpo extraño al ajustar por edad, sexo tipo de cuerpo extraño y maniobra de boca como medida de rescate. Este hallazgo es relevante debido a que pone en evidencia la importancia de una atención temprana, diagnóstico oportuno y manejo precoz en el paciente pediátrico.

Weaning Outcomes in Patients with Brain Injury.

BACKGROUND: Despite the need for specific weaning strategies in neurological patients, evidence is generally insufficient or lacking. We aimed to describe the evolution over time of weaning and extubation practices in patients with acute brain injury compared with patients who are mechanically ventilated (MV) due to other reasons. METHODS: We performed a secondary analysis of three prospective, observational, multicenter international studies conducted in 2004, 2010, and 2016 in adults who had need of invasive MV for more than 12 h. We collected data on baseline characteristics, variables related to management ventilator settings, and complications while patients were ventilated or until day 28. RESULTS: Among the 20,929 patients enrolled, we included 12,618 (60%) who started the weaning from MV, of whom 1722 (14%) were patients with acute brain injury. In the acutely brain-injured cohort, 538 patients (31%) did not undergo planned extubation, defined as the need for a tracheostomy without an attempt of extubation, accidental extubation, and death. Among the 1184 planned extubated patients with acute brain injury, 202 required reintubation (17%). Patients with acute brain injury had a higher odds for unplanned extubation (odds ratio [OR] 1.35, confidence interval for 95% [CI 95%] 1.19-1.54; p < 0.001), a higher odds of failure after the first attempt of weaning (spontaneous breathing trial or gradual reduction of ventilatory support; OR 1.14 [CI 95% 1.01-1.30; p = 0.03]), and a higher odds for reintubation (OR 1.41 [CI 95% 1.20-1.66; p < 0.001]) than patients without brain injury. Patients with hemorrhagic stroke had the highest odds for unplanned extubation (OR 1.47 [CI 95% 1.22-1.77; p < 0.001]), of failed extubation after the first attempt of weaning (OR 1.28 [CI 95% 1.06-1.55; p = 0.009]), and for reintubation (OR 1.49 [CI 95% 1.17-1.88; p < 0.001]). In relation to weaning evolution over time in patients with acute brain injury, the risk for unplanned extubation showed a downward trend; the risk for reintubation was not associated to time; and there was a significant increase in the percentage of patients who underwent extubation after the first attempt of weaning from MV. CONCLUSIONS: Patients with acute brain injury, compared with patients without brain injury, present higher odds of undergoing unplanned extubated after weaning was started, lower odds of being extubated after the first attempt, and a higher risk of reintubation.

Automated Computer-Assisted Image Analysis for the Fast Quantification of Kidney Fibrosis.

Chronic kidney disease (CKD) is a common and worldwide health problem and one of the most important causes of morbidity and mortality. Most primary research on this disease requires evaluating the fibrosis index in animal model kidneys, specifically using Masson's trichrome stain. Different programs are used to calculate the percentage of fibrosis; however, the analysis is time-consuming since one image must be performed at a time. CellProfiler™ is a program designed to analyze data obtained from biological samples and can process multiple images through pipelines, and the results can be exported to databases. This article explains how CellProfiler™ can be used to automatically analyze kidney histology photomicrographs from samples stained with Masson's trichrome stain to assess the percentage of fibrosis in an experimental animal model of CKD. A pipeline was created to analyze Masson's trichrome-stained slides in a model of CDK induced by adenine at doses of 50 mg/kg and 100 mg/kg, in addition to samples with the vehicle (75% glycerin). The results were compared with those obtained by ImageJ, and no significant differences were found between both programs. The CellProfiler™ pipeline made here is a reliable, fast, and easy alternative for kidney fibrosis analysis and quantification in experimental animal models.

Nanoparticles Formulation Improves the Antifibrogenic Effect of Quercetin on an Adenine-Induced Model of Chronic Kidney Disease.

Renal fibrosis is the final stage of chronic kidney injury characterized by glomerulosclerosis and tubulointerstitial fibrosis with parenchymal destruction. Quercetin belongs to the most studied flavonoids with antioxidant, anti-inflammatory, antifibrogenic, and antitumor activity. It modifies the TGF-ß/Smad signaling pathway, decreasing profibrogenic expression molecules and inducing the expression of antioxidant, anti-inflammatory, and antifibrogenic molecules. However, quercetin exhibits poor water solubility and low absorption and bioavailability. This limitation was solved by developing a nanoparticles formulation that improves the solubility and bioavailability of several bioactive compounds. Therefore, we aimed to investigate the in vivo antifibrogenic effect of a quercetin nanoparticles formulation. Male C57BL/6 mice were induced into chronic renal failure with 50 mg/kg of adenine for four weeks. The animals were randomly grouped and treated with 25, 50, or 100 mg/kg of quercetin, either macroparticles or nanoparticles formulation. We performed biochemical, histological, and molecular analyses to evaluate and compare the effect of macroparticles versus nanoparticles formulation on kidney damage. Here, we demonstrated that smaller doses of nanoparticles exhibited the same beneficial effect as larger doses of macroparticles on preventing kidney damage. This finding translates into less quercetin consumption reaching the desired therapeutic effect.

Long-term survival of mechanically ventilated patients with severe COVID-19: an observational cohort study.

BACKGROUND: Information is lacking regarding long-term survival and predictive factors for mortality in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) and undergoing invasive mechanical ventilation. We aimed to estimate 180-day mortality of patients with COVID-19 requiring invasive ventilation, and to develop a predictive model for long-term mortality. METHODS: Retrospective, multicentre, national cohort study between March 8 and April 30, 2020 in 16 intensive care units (ICU) in Spain. Participants were consecutive adults who received invasive mechanical ventilation for COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected in positive testing of a nasopharyngeal sample and confirmed by real time reverse-transcriptase polymerase chain reaction (rt-PCR). The primary outcomes was 180-day survival after hospital admission. Secondary outcomes were length of ICU and hospital stay, and ICU and in-hospital mortality. A predictive model was developed to estimate the probability of 180-day mortality. RESULTS: 868 patients were included (median age, 64 years [interquartile range [IQR], 56-71 years]; 72% male). Severity at ICU admission, estimated by SAPS3, was 56 points [IQR 50-63]. Prior to intubation, 26% received some type of noninvasive respiratory support. The unadjusted overall 180-day survival rates was 59% (95% CI 56-62%). The predictive factors measured during ICU stay, and associated with 180-day mortality were: age [Odds Ratio [OR] per 1-year increase 1.051, 95% CI 1.033-1.068)), SAPS3 (OR per 1-point increase 1.027, 95% CI 1.011-1.044), diabetes (OR 1.546, 95% CI 1.085-2.204), neutrophils to lymphocytes ratio (OR per 1-unit increase 1.008, 95% CI 1.001-1.016), failed attempt of noninvasive positive pressure ventilation prior to orotracheal intubation (OR 1.878 (95% CI 1.124-3.140), use of selective digestive decontamination strategy during ICU stay (OR 0.590 (95% CI 0.358-0.972) and administration of low dosage of corticosteroids (methylprednisolone 1 mg/kg) (OR 2.042 (95% CI 1.205-3.460). CONCLUSION: The long-term survival of mechanically ventilated patients with severe COVID-19 reaches more than 50% and may help to provide individualized risk stratification and potential treatments. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04379258. Registered 10 April 2020 (retrospectively registered).

Driving Pressure Is a Risk Factor for ARDS in Mechanically Ventilated Subjects Without ARDS.

BACKGROUND: Driving pressure (ΔP) has been described as a risk factor for mortality in patients with ARDS. However, the role of ΔP in the outcome of patients without ARDS and on mechanical ventilation has received less attention. Our objective was to evaluate the association between ΔP on the first day of mechanical ventilation with the development of ARDS. METHODS: This was a post hoc analysis of a multicenter, prospective, observational, international study that included subjects who were on mechanical ventilation for > 12 h. Our objective was to evaluate the association between ΔP on the first day of mechanical ventilation with the development of ARDS. To assess the effect of ΔP, a logistic regression analysis was performed when adjusting for other potential risk factors. Validation of the results obtained was performed by using a bootstrap method and by repeating the same analyses at day 2. RESULTS: A total of 1,575 subjects were included, of whom 65 (4.1%) developed ARDS. The ΔP was independently associated with ARDS (odds ratio [OR] 1.12, 95% CI 1.07-1.18 for each cm H2O of ΔP increase, P < .001). The same results were observed at day 2 (OR 1.14, 95% CI 1.07-1.21; P < .001) and after bootstrap validation (OR 1.13, 95% CI 1.04-1.22; P < .001). When taking the prevalence of ARDS in the lowest quartile of ΔP (≤9 cm H2O) as a reference, the subjects with ΔP > 12-15 cm H2O and those with ΔP > 15 cm H2O presented a higher probability of ARDS (OR 3.65, 95% CI 1.32-10.04 [P = .01] and OR 7.31, 95% CI, 2.89-18.50 [P < .001], respectively). CONCLUSIONS: In the subjects without ARDS, a higher level of ΔP on the first day of mechanical ventilation was associated with later development of ARDS. (ClinicalTrials.gov registration NCT02731898.).

Can Transcranial Direct Current Stimulation Enhance Functionality in Older Adults? A Systematic Review.

Transcranial direct current stimulation (tDCS) is a non-invasive, easy to administer, well-tolerated, and safe technique capable of affecting brain excitability, both at the cortical and cerebellum levels. However, its effectiveness has not been sufficiently assessed in all population segments or clinical applications. This systematic review aimed at compiling and summarizing the currently available scientific evidence about the effect of tDCS on functionality in older adults over 60 years of age. A search of databases was conducted to find randomized clinical trials that applied tDCS versus sham stimulation in the above-mentioned population. No limits were established in terms of date of publication. A total of 237 trials were found, of which 24 met the inclusion criteria. Finally, nine studies were analyzed, including 260 healthy subjects with average age between 61.0 and 85.8 years. Seven of the nine included studies reported superior improvements in functionality variables following the application of tDCS compared to sham stimulation. Anodal tDCS applied over the motor cortex may be an effective technique for improving balance and posture control in healthy older adults. However, further high-quality randomized controlled trials are required to determine the most effective protocols and to clarify potential benefits for older adults.

Machine learning predicts mortality based on analysis of ventilation parameters of critically ill patients: multi-centre validation.

BACKGROUND: Mechanical Ventilation (MV) is a complex and central treatment process in the care of critically ill patients. It influences acid-base balance and can also cause prognostically relevant biotrauma by generating forces and liberating reactive oxygen species, negatively affecting outcomes. In this work we evaluate the use of a Recurrent Neural Network (RNN) modelling to predict outcomes of mechanically ventilated patients, using standard mechanical ventilation parameters. METHODS: We performed our analysis on VENTILA dataset, an observational, prospective, international, multi-centre study, performed to investigate the effect of baseline characteristics and management changes over time on the all-cause mortality rate in mechanically ventilated patients in ICU. Our cohort includes 12,596 adult patients older than 18, associated with 12,755 distinct admissions in ICUs across 37 countries and receiving invasive and non-invasive mechanical ventilation. We carry out four different analysis. Initially we select typical mechanical ventilation parameters and evaluate the machine learning model on both, the overall cohort and a subgroup of patients admitted with respiratory disorders. Furthermore, we carry out sensitivity analysis to evaluate whether inclusion of variables related to the function of other organs, improve the predictive performance of the model for both the overall cohort as well as the subgroup of patients with respiratory disorders. RESULTS: Predictive performance of RNN-based model was higher with Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of 0.72 (± 0.01) and Average Precision (AP) of 0.57 (± 0.01) in comparison to RF and LR for the overall patient dataset. Higher predictive performance was recorded in the subgroup of patients admitted with respiratory disorders with AUC of 0.75 (± 0.02) and AP of 0.65 (± 0.03). Inclusion of function of other organs further improved the performance to AUC of 0.79 (± 0.01) and AP 0.68 (± 0.02) for the overall patient dataset and AUC of 0.79 (± 0.01) and AP 0.72 (± 0.02) for the subgroup with respiratory disorders. CONCLUSION: The RNN-based model demonstrated better performance than RF and LR in patients in mechanical ventilation and its subgroup admitted with respiratory disorders. Clinical studies are needed to evaluate whether it impacts decision-making and patient outcomes. TRIAL REGISTRATION: NCT02731898 ( https://clinicaltrials.gov/ct2/show/NCT02731898 ), prospectively registered on April 8, 2016.

Evolution Over Time of Ventilatory Management and Outcome of Patients With Neurologic Disease.

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease.

Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. METHODS: Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p < 0·05 was considered as unstable). RESULTS: Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16-24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. CONCLUSION: Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. TRIAL REGISTRATION: The study was registered with Clinical trials.gov Identifier: NCT04534569.

Propensity-Adjusted Comparison of Mortality of Elderly Versus Very Elderly Ventilated Patients.

BACKGROUND: The growing proportion of elderly intensive care patients constitutes a public health challenge. The benefit of critical care in these patients remains unclear. We compared outcomes in elderly versus very elderly subjects receiving mechanical ventilation. METHODS: In total, 5,557 mechanically ventilated subjects were included in our post hoc retrospective analysis, a subgroup of the VENTILA study. We divided the cohort into 2 subgroups on the basis of age: very elderly subjects (age ≥ 80 y; n = 1,430), and elderly subjects (age 65-79 y; n = 4,127). A propensity score on being very elderly was calculated. Evaluation of associations with 28-d mortality was done with logistic regression analysis. RESULTS: Very elderly subjects were clinically sicker as expressed by higher SAPS II scores (53 ± 18 vs 50 ± 18, P < .001), and their rates of plateau pressure < 30 cm H2O were higher, whereas other parameters did not differ. The 28-d mortality was higher in very elderly subjects (42% vs 34%, P < .001) and remained unchanged after propensity score adjustment (adjusted odds ratio 1.31 [95% CI 1.16-1.49], P < .001). CONCLUSIONS: Age was an independent and unchangeable risk factor for death in mechanically ventilated subjects. However, survival rates of very elderly subjects were > 50%. Denial of critical care based solely on age is not justified. (ClinicalTrials.gov registration NCT02731898.).

Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study.

BACKGROUND: Current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS). METHODS: An international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared. FINDINGS: 12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved. INTERPRETATION: More than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.

Diagnostic accuracy of portable chest radiograph in mechanically ventilated patients when compared with autopsy findings.

PURPOSE: Evaluate diagnostic accuracy of portable chest radiograph in mechanically ventilated patients taking autopsy findings as the gold standard and the interobserver agreement among intensivists and radiologists. MATERIALS AND METHODS: Retrospective study of 422 patients over 22 years who died in the ICU, underwent an autopsy, and had at least one portable chest radiograph 72 h prior to death. Two intensivists and two radiologists independently read each chest radiograph. Sensitivity, specificity, positive and negative likelihood ratios were evaluated. Overall performance metrics accuracy between intensivists and radiologists were compared using a generalized estimating equation. Cohen's kappa coefficient was used to evaluate the interobserver agreement with the following values: <0.20:poor, 0.21-0.40:fair, 0.41-0.60:moderate, 0.61-0.80:good, 0.81-1.00:excellent. RESULTS: Overall sensitivity and specificity for pneumonia was 24% and 91% respectively. Overall sensitivity and specificity for ARDS was 68% and 74% respectively. Sensitivity for pneumonia was higher among radiologists (p < 0,05). Specificity for ADRS was higher among radiologists (p < 0,05). Good interobserver agreement among radiologists and poor correlation between intensivists was found. CONCLUSIONS: Chest radiographs has a moderate specificity for ARDS and a high specificity for pneumonia, with limited sensitivity in both entities. Interobserver agreement of portable chest radiograph in the mechanically ventilated patients is higher between radiologists than intensivists.

Inter-country variability over time in the mortality of mechanically ventilated patients.

PURPOSE: Variations in clinical characteristics and management and in the mortality of mechanically ventilated patients have not been sufficiently evaluated. We hypothesized that mortality shows a variability associated with country after adjustment for clinical characteristics and management. METHODS: Analysis of four studies carried out at 6-year intervals over an 18-year period. The studies included 26,024 patients (5183 in 1998, 4968 in 2004, 8108 in 2010, and 7765 in 2016) admitted to 1253 units from 38 countries. The primary outcome was 28-day mortality. We performed analyses using multilevel logistic modeling with mixed-random effects, including country as a random variable. To evaluate the effect of management strategies on mortality, a mediation analysis was performed. RESULTS: Adjusted 28-day mortality decreased significantly over time (first study as reference): 2004: odds ratio 0.82 (95% confidence interval [CI] 0.72-0.93); 2010: 0.63 (95% CI 0.53-0.75); 2016: 0.49 (95% CI 0.39-0.61). A protective ventilatory strategy and the use of continuous sedation mediated a moderate fraction of the effect of time on mortality in patients with moderate hypoxemia and without hypoxemia, respectively. Logistic multilevel modeling showed a significant effect of country on mortality: median odds ratio (MOR) in 1998: 2.02 (95% CI 1.57-2.48); in 2004: 1.76 (95% CI 1.47-2.06); in 2010: 1.55 (95% CI 1.37-1.74), and in 2016: 1.39 (95% CI 1.25-1.54). CONCLUSIONS: These findings suggest that country could contribute, independently of confounder variables, to outcome. The magnitude of the effect of country decreased over time. Clinical trials registered with http://www.clinicaltrials.gov (NCT02731898).

Easy prognostic assessment of concomitant organ failure in critically ill patients undergoing mechanical ventilation.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening disease. We evaluated the prognostic utility of Model for End-stage Liver Disease excluding INR (MELD-XI) score for predicting mortality in a cohort of critically ill patients on mechanical ventilation. METHODS: In total, 11,091 mechanically ventilated patients were included in our post-hoc retrospective analysis, a subgroup of the VENTILA study (NCT02731898). Evaluation of associations with mortality was done by logistic and Cox regression analysis, an optimal cut-off was calculated using the Youden Index. We divided the cohort in two sub-groups based on their MELD-XI score at the optimal cut-off (12 score points). RESULTS: Peak-, plateau- and positive end-expiratory pressure were higher in patients with MELD-XI>12. Patients with MELD-XI>12 had higher driving pressures (14 ±â€¯6 cmH2O versus 13 ±â€¯6; p < 0.001). MELD-XI was associated with 28-day mortality after correction for relevant cofounders including SAPS II and ventilation pressures (HR 1.04 95%CI 1.03-1.05; p < 0.001. Patients with MELD-XI>12 evidenced both increased hospital (46% versus 27%; p < 0.001) and 28-day mortality (39% versus 22%). CONCLUSIONS: MELD-XI is independently associated with mortality and constitutes a useful and easily applicable tool for risk stratification in critically ill patients receiving mechanical ventilation. TRIAL REGISTRATION: NCT02731898, registered 4 April 2016.

Invasive aspergillosis in critically ill patients: An autopsy study.

Autopsy studies show that IA is among the most commonly missed diagnoses in critically ill patients. And, because of lack of unequivocal diagnostic criteria, a timely diagnosis remains challenging. We investigate the epidemiology of and the clinical risk factors for IA in critically ill patients. We conducted a retrospective, observational study of all consecutive ICU patients with evidence of IA in the postmortem examination. During the period of the study (25 years), 893 postmortem examinations were performed in the ICU. Twenty-five patients (2.8%) were diagnosed with IA in autopsy. Only ten (40%) were classified as IA ante-mortem, based on the initiation of antifungal treatment. The most common comorbid conditions were corticosteroid treatment (n = 14, 56%), chronic obstructive pulmonary disease (COPD) (n = 11, 44%), immunosuppression (n = 6, 24%) and haematological malignancy (n = 5, 20%). Twenty-three patients (92%) had three or more risk factors for IA. Critically ill patients with pulmonary infiltrates, treated with high doses intravenous corticosteroids (even for a short period of time), particularly COPD patients who developed worsening respiratory insufficiency despite appropriate treatment were at the highest risk of IA.