Typical phenotypes of patients with acute respiratory failure with and without COVID-19 and their relationship with outcomes: a cohort study / Fenótipos característicos em pacientes com insuficiência respiratória aguda com e sem COVID-19 e sua relação com os desfechos: um estudo de coorte

ABSTRACT Objective: To compare, within a cohort of patients with acute respiratory failure, the phenotypes of patients with and without COVID-19 in the context of the pandemic and evaluate whether COVID-19 is an independent predictor of intensive care unit mortality. Methods: This historical cohort study evaluated 1001 acute respiratory failure patients with suspected COVID-19 admitted to the intensive care unit of 8 hospitals. Patients were classified as COVID-19 cases and non-COVID-19 cases according to real-time polymerase chain reaction results. Data on clinical and demographic characteristics were collected on intensive care unit admission, as well as daily clinical and laboratory data and intensive care unit outcomes. Results: Although the groups did not differ in terms of APACHE II or SOFA scores at admission, the COVID-19 group had more initial symptoms of fever, myalgia and diarrhea, had a longer duration of symptoms, and had a higher prevalence of obesity. They also had a lower PaO2/FiO2 ratio, lower platelet levels than non-COVID-19 patients, and more metabolic changes, such as higher levels of blood glucose, C-reactive protein, and lactic dehydrogenase. Patients with non-COVID-19 acute respiratory failure had a higher prevalence of chronic obstructive pulmonary disease/asthma and cardiopathy. Patients with COVID-19 stayed in the hospital longer and had more complications, such as acute kidney failure, severe acute respiratory distress syndrome and severe infection. The all-cause mortality rate was also higher in this group (43.7% in the COVID-19 group versus 27.4% in the non-COVID-19 group). The diagnosis of COVID-19 was a predictor of intensive care unit mortality (odds ratio, 2.77; 95%CI, 1.89 - 4.07; p < 0.001), regardless of age or Charlson Comorbidity Index score. Conclusion: In a prospective cohort of patients admitted with acute respiratory failure, patients with COVID-19 had a clearly different phenotype and a higher mortality than non-COVID-19 patients. This may help to outline more accurate screening and appropriate and timely treatment for these patients.

RESUMO Objetivo: Comparar, em uma coorte de pacientes com insuficiência respiratória aguda, os fenótipos de pacientes com e sem COVID-19, no contexto da pandemia, e avaliar se a COVID-19 é um preditor independente de mortalidade na unidade de terapia intensiva. Métodos: Este estudo de coorte histórico avaliou 1.001 pacientes com insuficiência respiratória aguda e suspeita de COVID-19 internados na unidade de terapia intensiva de oito hospitais. Os pacientes foram classificados como casos com e sem COVID-19 segundo os resultados da RT-PCR. Foram coletados dados sobre características clínicas e demográficas na admissão à unidade de terapia intensiva, bem como dados clínicos e laboratoriais diários e desfechos da unidade de terapia intensiva. Resultados: Embora os grupos não tenham diferido nos escores APACHE II ou SOFA na admissão, o grupo COVID-19 apresentou mais sintomas iniciais de febre, mialgia e diarreia e teve maior duração dos sintomas e maior prevalência de obesidade. Eles também apresentaram menor relação PaO2/FiO2 e níveis mais baixos de plaquetas do que os pacientes sem COVID-19 e mais alterações metabólicas, como níveis mais altos de glicemia, proteína C-reativa e desidrogenase lática. Os pacientes com insuficiência respiratória aguda sem COVID-19 apresentaram maior prevalência de doença pulmonar obstrutiva crônica/asma e cardiopatia. Os pacientes com COVID-19 permaneceram mais tempo no hospital e tiveram mais complicações, como insuficiência renal aguda, síndrome do desconforto respiratório agudo grave e infecção grave. A taxa de mortalidade por todas as causas também foi maior nesse grupo (43,7% no grupo com COVID-19 versus 27,4% no grupo sem COVID-19). O diagnóstico de COVID-19 foi um preditor de mortalidade na unidade de terapia intensiva (razão de chances de 2,77; IC95% 1,89 - 4,07; p < 0,001), independentemente da idade ou da pontuação do Índice de Comorbidade de Charlson. Conclusão: Em uma coorte prospectiva de pacientes admitidos com insuficiência respiratória aguda, os pacientes com COVID-19 apresentaram fenótipo claramente diferente e uma mortalidade mais alta do que os pacientes sem COVID-19. Isso pode ajudar a traçar uma triagem mais precisa e um tratamento adequado e oportuno para esses pacientes.

Tracheal regeneration with acellular human amniotic membrane and 15-deoxy-∆12,14prostaglandinj2 nanoparticles in a rabbit model.

The treatment of tracheal pathologies remains challenging.Nanotechnology allows adding substances to decellularized human amniotic membrane (DHAM), such as 15-Deoxy-∆12,14ProstaglandinJ2 nanoparticles (15D-PGJ2-NC).This study performed a tracheotomy in rabbits randomized into three groups.The tissue repair process was evaluated when treated with DHAM associated or not with 15D-PGJ2-NC.The average of the area in the control group was 54.76% smaller than DHAM group and 41.98% smaller than DHAM + 15D-PGJ2-NC group (p=0.004 for both).The DHAM + 15D-PGJ2-NC group had significantly more immature cartilage (p=0.015).DHAM impregnated with 15D-PGJ2-NC could provide support for the healing of the tracheal defect and may prevent reduction of its lumen.

Histological, Laboratorial, and Clinical Benefits of an Optimized Maintenance Strategy of a Potential Organ Donor-A Rabbit Experimental Model.

INTRODUCTION: Most transplanted organs are obtained from brain-dead donors. Inflammation results in a higher rate of rejection. Objectives: The objective of this animal model of brain death (BD) was to evaluate the effect of the progressive institution of volume expansion, norepinephrine, and combined hormone therapy on clinical, laboratory, and histological aspects. Methods: Twenty rabbits were divided: A (control), B (induction of BD + infusion of crystalloid), C (BD + infusion of crystalloid and noradrenaline (NA)), and D (BD + infusion of crystalloid + vasopressin + levothyroxine + methylprednisolone + NA). The animals were monitored for four hours with consecutives analysis of vital signs and blood samples. The organs were evaluated by a pathologist. Results: In Group D, we observed fewer number and lesser volume of infusions (p = 0.032/0.014) when compared with groups B and C. Mean arterial pressure levels were higher in group D when compared with group B (p = 0.008). Group D had better glycemic control when compared with group C (p = 0.016). Sodium values were elevated in group B in relation to groups C and D (p = 0.021). In Group D, the organ perfusion was better. Conclusion: The optimized strategy of management of BD animals is associated with better hemodynamic, glycemic, and natremia control, besides reducing early signs of ischemia.

Typical phenotypes of patients with acute respiratory failure with and without COVID-19 and their relationship with outcomes: a cohort study.

OBJECTIVE: To compare, within a cohort of patients with acute respiratory failure, the phenotypes of patients with and without COVID-19 in the context of the pandemic and evaluate whether COVID-19 is an independent predictor of intensive care unit mortality. METHODS: This historical cohort study evaluated 1001 acute respiratory failure patients with suspected COVID-19 admitted to the intensive care unit of 8 hospitals. Patients were classified as COVID-19 cases and non-COVID-19 cases according to real-time polymerase chain reaction results. Data on clinical and demographic characteristics were collected on intensive care unit admission, as well as daily clinical and laboratory data and intensive care unit outcomes. RESULTS: Although the groups did not differ in terms of APACHE II or SOFA scores at admission, the COVID-19 group had more initial symptoms of fever, myalgia and diarrhea, had a longer duration of symptoms, and had a higher prevalence of obesity. They also had a lower PaO2/FiO2 ratio, lower platelet levels than non-COVID-19 patients, and more metabolic changes, such as higher levels of blood glucose, C-reactive protein, and lactic dehydrogenase. Patients with non-COVID-19 acute respiratory failure had a higher prevalence of chronic obstructive pulmonary disease/asthma and cardiopathy. Patients with COVID-19 stayed in the hospital longer and had more complications, such as acute kidney failure, severe acute respiratory distress syndrome and severe infection. The all-cause mortality rate was also higher in this group (43.7% in the COVID-19 group versus 27.4% in the non-COVID-19 group). The diagnosis of COVID-19 was a predictor of intensive care unit mortality (odds ratio, 2.77; 95%CI, 1.89 - 4.07; p < 0.001), regardless of age or Charlson Comorbidity Index score. CONCLUSION: In a prospective cohort of patients admitted with acute respiratory failure, patients with COVID-19 had a clearly different phenotype and a higher mortality than non-COVID-19 patients. This may help to outline more accurate screening and appropriate and timely treatment for these patients.

Epidemiologia e desfecho dos pacientes de alto risco cirúrgico admitidos em unidades de terapia intensiva no Brasil / Epidemiology and outcome of high-surgical-risk patients admitted to an intensive care unit in Brazil

RESUMO Objetivo: Definir o perfil epidemiológico e os principais determinantes de morbimortalidade dos pacientes cirúrgicos não cardíacos de alto risco no Brasil. Métodos: Estudo prospectivo, observacional e multicêntrico. Todos os pacientes cirúrgicos não cardíacos admitidos nas unidades de terapia intensiva, ou seja, considerados de alto risco, no período de 1 mês, foram avaliados e acompanhados diariamente por, no máximo, 7 dias na unidade de terapia intensiva, para determinação de complicações. As taxas de mortalidade em 28 dias de pós-operatório, na unidade de terapia intensiva e hospitalar foram avaliadas. Resultados: Participaram 29 unidades de terapia intensiva onde foram realizadas cirurgias em 25.500 pacientes, dos quais 904 (3,5%) de alto risco (intervalo de confiança de 95% - IC95% 3,3% - 3,8%), tendo sido incluídos no estudo. Dos pacientes envolvidos, 48,3% eram de unidades de terapia intensiva privadas e 51,7% de públicas. O tempo de internação na unidade de terapia intensiva foi de 2,0 (1,0 - 4,0) dias e hospitalar de 9,5 (5,4 - 18,6) dias. As taxas de complicações foram 29,9% (IC95% 26,4 - 33,7) e mortalidade em 28 dias pós-cirurgia 9,6% (IC95% 7,4 - 12,1). Os fatores independentes de risco para complicações foram Simplified Acute Physiology Score 3 (SAPS 3; razão de chance − RC = 1,02; IC95% 1,01 - 1,03) e Sequential Organ Failure Assessment Score (SOFA) da admissão na unidade de terapia intensiva (RC =1,17; IC95% 1,09 - 1,25), tempo de cirurgia (RC = 1,001; IC95% 1,000 - 1,002) e cirurgias de emergências (RC = 1,93; IC95% 1,10 - 3,38). Em adição, foram associados com mortalidade em 28 dias idade (RC = 1,032; IC95% 1,011 - 1,052) SAPS 3 (RC = 1,041; IC95% 1,107 - 1,279), SOFA (RC = 1,175; IC95% 1,069 - 1,292) e cirurgias emergenciais (RC = 2,509; IC95% 1,040 - 6,051). Conclusão: Pacientes com escores prognósticos mais elevados, idosos, tempo cirúrgico e cirurgias emergenciais estiveram fortemente associados a maior mortalidade em 28 dias e mais complicações durante permanência em unidade de terapia intensiva.

ABSTRACT Objective: To define the epidemiological profile and the main determinants of morbidity and mortality in noncardiac high surgical risk patients in Brazil. Methods: This was a prospective, observational and multicenter study. All noncardiac surgical patients admitted to intensive care units, i.e., those considered high risk, within a 1-month period were evaluated and monitored daily for a maximum of 7 days in the intensive care unit to determine complications. The 28-day postoperative, intensive care unit and hospital mortality rates were evaluated. Results: Twenty-nine intensive care units participated in the study. Surgeries were performed in 25,500 patients, of whom 904 (3.5%) were high-risk (95% confidence interval - 95%CI 3.3% - 3.8%) and were included in the study. Of the participating patients, 48.3% were from private intensive care units, and 51.7% were from public intensive care units. The length of stay in the intensive care unit was 2.0 (1.0 - 4.0) days, and the length of hospital stay was 9.5 (5.4 - 18.6) days. The complication rate was 29.9% (95%CI 26.4 - 33.7), and the 28-day postoperative mortality rate was 9.6% (95%CI 7.4 - 12.1). The independent risk factors for complications were the Simplified Acute Physiology Score 3 (SAPS 3; odds ratio - OR = 1.02; 95%CI 1.01 - 1.03) and Sequential Organ Failure Assessment Score (SOFA) on admission to the intensive care unit (OR = 1.17; 95%CI 1.09 - 1.25), surgical time (OR = 1.001, 95%CI 1.000 - 1.002) and emergency surgeries (OR = 1.93, 95%CI, 1.10 - 3.38). In addition, there were associations with 28-day mortality (OR = 1.032; 95%CI 1.011 - 1.052), SAPS 3 (OR = 1.041; 95%CI 1.107 - 1.279), SOFA (OR = 1.175, 95%CI 1.069 - 1.292) and emergency surgeries (OR = 2.509; 95%CI 1.040 - 6.051). Conclusion: Higher prognostic scores, elderly patients, longer surgical times and emergency surgeries were strongly associated with higher 28-day mortality and more complications during the intensive care unit stay.

In vitro differentiation capacity of human breastmilk stem cells: A systematic review.

BACKGROUND: Mesenchymal stem cells are pluripotent cells that have the ability to generate cells from a cell line or in other cell types from different tissues but from the same origin. Although those cells have more limited differentiation capacity than embryonic stem cells, they are easily obtained from somatic tissue and can be grown in large quantities. This characteristic of undifferentiated stem cells differentiating into different cell lines arouses strategies in regenerative medicine for the treatment of different diseases such as neurodegenerative diseases. AIM: To evaluate the cell differentiation capacity of human breastmilk stem cells for the three germ layers by a systematic review. METHODS: The searched databases were PubMed, EMBASE, OVID, and COCHRANE LIBRARY, published between 2007 and 2018 in the English language. All were in vitro studies for analysis of the "cell differentiation potential" in the literature using the keywords "human breastmilk," "stem cells," and keywords combined with the Boolean operator "NOT" were used to exclude those articles that had the word "CANCER" and their respective synonyms, which were previously consulted according to medical subject heading terms. PRISMA 2009 guidelines were followed in this study. RESULTS: A total of 315 titles and abstracts of articles were examined. From these, 21 were in common with more than one database, leaving 294 articles for analysis. Of that total, five publications met the inclusion criteria. When analyzing the publications, it was demonstrated that human breastmilk stem cells have a high cellular plasticity, exhibiting the ability to generate cells of all three germ layers, endoderm, mesoderm, and ectoderm, demonstrating their stemness. Those cells expressed the genes, TRA-1-60/81, octamer-binding transcription factor 4, and NANOG, of which NANOG, a critical regulator for self-renewal and maintenance, was the most highly expressed. Those cells have the ability to differentiate in vitro into adipocytes, chondrocytes, osteocytes, oligodendrocytes, astrocytes, and neurons as well hepatocytes, ß-pancreatic cells, and cardiomyocytes. CONCLUSION: Although the literature has been scarce, the pluripotentiality of these cells represents great potential for tissue engineering and cellular therapy. Further studies for safe clinical translation are needed.

Sialochemical analysis in polytraumatized patients in intensive care units.

The profiles of polytraumatized patients in intensive care units were characterized. Serum and salivary markers were compared with normality between Classes I and II of APACHE II and between periods of hospitalization; these results were correlated. This was a prospective study on saliva charts and collection (n = 70). Profile: male, 27 years old, blunt traumas and collisions. Serum parameters with normality: decrease in pH, creatinine at admission to Class I, and at 48 and 72 hours in both classes; K+ at 48 h in Class II; Ca+ on admission in both classes and at 72 h in Class I. Increase in urea at 72 h in Class II, glucose at all times and in all classes, and Ca+ at 48 h in both classes. Class II had high Na+ at 48 and 72 h compared to Class I. In Class I, creatinine reduction occurred in 48 h and 72 h compared to admission and an increase of Ca+ at 48 h with admission. In Class II, pH and Na+ increased at 48 h and 72 h compared to admission. K+ decreased from admission to 48 h and increased from 48 h to 72 h. Urea increased from 48 to 72 hours. Creatinine decreased from admission to 48 and 72 hours. Ca+ increased from admission to 48 hours and decreased from 48 to 72 hours. There was an increase in the saliva levels in both classes and times in relation to normality. There was an increase in urea at admission, glucose at 72 h, and Ca+ at 48 h in Class II compared with Class I. Class I urea increased from admission to 48 h and Ca+ decreased from admission to 48 h. Class II urea decreased from 48 h to 72 h. Strong or very strong positive correlation was identified between blood and creatinine saliva at all times and regular and negative Ca+ at 72 h. This study provides evidence that salivary and serum biomarkers can be used together to monitor the evolution of the clinical symptoms of ICU patients.

Guidelines for the assessment and acceptance of potential brain-dead organ donors. / Diretrizes para avaliação e validação do potencial doador de órgãos em morte encefálica.

Organ transplantation is the only alternative for many patients with terminal diseases. The increasing disproportion between the high demand for organ transplants and the low rate of transplants actually performed is worrisome. Some of the causes of this disproportion are errors in the identification of potential organ donors and in the determination of contraindications by the attending staff. Therefore, the aim of the present document is to provide guidelines for intensive care multi-professional staffs for the recognition, assessment and acceptance of potential organ donors.

Diretrizes para avaliação e validação do potencial doador de órgãos em morte encefálica / Guidelines for the assessment and acceptance of potential brain-dead organ donors

RESUMO O transplante de órgãos é a única alternativa para muitos pacientes portadores de algumas doenças terminais. Ao mesmo tempo, é preocupante a crescente desproporção entre a alta demanda por transplantes de órgãos e o baixo índice de transplantes efetivados. Dentre as diferentes causas que alimentam essa desproporção, estão os equívocos na identificação do potencial doador de órgãos e as contraindicações mal atribuídas pela equipe assistente. Assim, o presente documento pretende fornecer subsídios à equipe multiprofissional da terapia intensiva para o reconhecimento, a avaliação e a validação do potencial doador de órgãos.

ABSTRACT Organ transplantation is the only alternative for many patients with terminal diseases. The increasing disproportion between the high demand for organ transplants and the low rate of transplants actually performed is worrisome. Some of the causes of this disproportion are errors in the identification of potential organ donors and in the determination of contraindications by the attending staff. Therefore, the aim of the present document is to provide guidelines for intensive care multi-professional staffs for the recognition, assessment and acceptance of potential organ donors.

Pacientes com infecção por vírus A (H1N1) admitidos em unidades de terapia intensiva do Estado do Paraná, Brasil / Outcome of influenza A (H1N1) patients admitted to intensive care units in the Paraná state, Brazil

OBJETIVO: Analisar a evolução, características clínico-epidemiológicas e fatores de gravidade em pacientes adultos admitidos com diagnóstico de infecção por vírus A(H1N1) em unidades de terapia intensiva públicas e privadas no Estado do Paraná, sul do Brasil. MÉTODOS: Estudo coorte de análise de prontuários de pacientes com idade superior a 12 anos admitidos em 11 unidades de terapia intensiva de 6 cidades no Estado do Paraná (Brasil), durante um período de 45 dias, com diagnóstico de gripe suína. O diagnóstico de infecção por vírus A(H1N1) foi feito através de real time -polimerase chain reaction (RT-PCR) da secreção nasofaríngea, ou de forte suspeita clínica quando descartadas outras causas (mesmo com RT-PCR negativo). Foi feita estatística descritiva e análise com teste chi quadrado, para comparação entre porcentagens e teste t de student para variáveis continuas, com análise univariada, admitindo-se como significante um p<0,05. RESULTADOS: Foram admitidos 63 pacientes adultos com diagnóstico de H1N1, sendo 37 (58,7 por cento) RT-PCR positivos. A maioria dos pacientes era de adultos jovens (65 por cento com idade inferior a 40 anos), sem predominância de sexo e alta incidência de obesidade (27,0 por cento com índice de massa corpórea>30). A média do escore Acute Physiologic Chronic Heatlh Evaluation II (APACHE II) foi de 15,0 ± 8,1. A mortalidade na unidade de terapia intensiva foi de 39,7 por cento. Os principais fatores associados a essa mortalidade foram exame positivo no teste RT-PCR, níveis baixos de relação PaO2/FiO2 inicial, níveis elevados de uréia e desidrogenase lática iniciais, nível de pressão expiratória final positiva necessária, necessidade de posição prona e de drogas vasopressoras. CONCLUSÕES: Pacientes admitidos em unidades de terapia intensiva com infecção por vírus A(H1N1) apresentaram alto risco de óbito, particularmente devidos ao comprometimento respiratório. O exame RT-PCR positivo, níveis de uréia e de desidrogenase ...

OBJECTIVE: This study aimed to analyze outcome, clinical and epidemiological characteristics and severity factors in adult patients admitted with a diagnosis of infection by virus A (H1N1) to public and private intensive care units, in Paraná, Brazil. METHODS: Cohort study of medical charts of patients older than 12 years admitted to 11 intensive care units in 6 cities in the state of Parana, Brazil, during a period of 45 days, with diagnosis of swine influenza. The diagnosis of infection with A (H1N1) was made by real time polymerase chain reaction (RT-PCR) of nasopharyngeal secretion, or strong clinical suspicion when other causes had been ruled out (even with negative RT-PCR). Descriptive statistics were performed, analysis by the Chi square test was used to compare percentages and the Student's t test for continuous variables with univariate analysis, assuming a significance level of p <0.05. RESULTS: There were 63 adult patients admitted with a diagnosis of H1N1, 37 (58.7 percent) being RT-PCR positive. Most patients were young adults (65 percent under 40 years of age) with no gender predominance and high incidence of obesity (27.0 percent with Body Mass Index > 30). Mean of the Acute Physiologic Chronic Health Evaluation II (APACHE II) score was 15.0 + 8.1. Mortality in the intensive care unit was 39.7 percent. The main factors associated with mortality were: positive RT-PCR, low levels of initial PaO2/FiO2, high initial levels of urea and lactate dehydrogenase, required level of positive end expiratory pressure, need for the prone position and vasopressors. CONCLUSIONS: Adult patients with A (H1N1) virus infection admitted to intensive care units had a high risk of death, particularly due to respiratory impairment. Positive RT-PCR, urea and lactic dehydrogenase, low initial PaO2/FiO2 and high levels of PEEP were correlated with higher mortality.

Outcome of influenza A (H1N1) patients admitted to intensive care units in the Paraná state, Brazil. / Pacientes com infecção por vírus A (H1N1) admitidos em unidades de terapia intensiva do Estado do Paraná, Brasil.

OBJECTIVE: This study aimed to analyze outcome, clinical and epidemiological characteristics and severity factors in adult patients admitted with a diagnosis of infection by virus A (H1N1) to public and private intensive care units, in Paraná, Brazil. METHODS: Cohort study of medical charts of patients older than 12 years admitted to 11 intensive care units in 6 cities in the state of Parana, Brazil, during a period of 45 days, with diagnosis of swine influenza. The diagnosis of infection with A (H1N1) was made by real time polymerase chain reaction (RT-PCR) of nasopharyngeal secretion, or strong clinical suspicion when other causes had been ruled out (even with negative RT-PCR). Descriptive statistics were performed, analysis by the Chi square test was used to compare percentages and the Student's t test for continuous variables with univariate analysis, assuming a significance level of p <0.05. RESULTS: There were 63 adult patients admitted with a diagnosis of H1N1, 37 (58.7%) being RT-PCR positive. Most patients were young adults (65% under 40 years of age) with no gender predominance and high incidence of obesity (27.0% with Body Mass Index > 30). Mean of the Acute Physiologic Chronic Health Evaluation II (APACHE II) score was 15.0 + 8.1. Mortality in the intensive care unit was 39.7%. The main factors associated with mortality were: positive RT-PCR, low levels of initial PaO2/FiO2, high initial levels of urea and lactate dehydrogenase, required level of positive end expiratory pressure, need for the prone position and vasopressors. CONCLUSIONS: Adult patients with A (H1N1) virus infection admitted to intensive care units had a high risk of death, particularly due to respiratory impairment. Positive RT-PCR, urea and lactic dehydrogenase, low initial PaO2/FiO2 and high levels of PEEP were correlated with higher mortality.