Discovery of antimicrobial peptides in the global microbiome with machine learning.

Novel antibiotics are urgently needed to combat the antibiotic-resistance crisis. We present a machine-learning-based approach to predict antimicrobial peptides (AMPs) within the global microbiome and leverage a vast dataset of 63,410 metagenomes and 87,920 prokaryotic genomes from environmental and host-associated habitats to create the AMPSphere, a comprehensive catalog comprising 863,498 non-redundant peptides, few of which match existing databases. AMPSphere provides insights into the evolutionary origins of peptides, including by duplication or gene truncation of longer sequences, and we observed that AMP production varies by habitat. To validate our predictions, we synthesized and tested 100 AMPs against clinically relevant drug-resistant pathogens and human gut commensals both in vitro and in vivo. A total of 79 peptides were active, with 63 targeting pathogens. These active AMPs exhibited antibacterial activity by disrupting bacterial membranes. In conclusion, our approach identified nearly one million prokaryotic AMP sequences, an open-access resource for antibiotic discovery.

The use of natural language processing in palliative care research: A scoping review.

BACKGROUND: Natural language processing has been increasingly used in palliative care research over the last 5 years for its versatility and accuracy. AIM: To evaluate and characterize natural language processing use in palliative care research, including the most commonly used natural language processing software and computational methods, data sources, trends in natural language processing use over time, and palliative care topics addressed. DESIGN: A scoping review using the framework by Arksey and O'Malley and the updated recommendations proposed by Levac et al. was conducted. SOURCES: PubMed, Web of Science, Embase, Scopus, and IEEE Xplore databases were searched for palliative care studies that utilized natural language processing tools. Data on study characteristics and natural language processing instruments used were collected and relevant palliative care topics were identified. RESULTS: 197 relevant references were identified. Of these, 82 were included after full-text review. Studies were published in 48 different journals from 2007 to 2022. The average sample size was 21,541 (median 435). Thirty-two different natural language processing software and 33 machine-learning methods were identified. Nine main sources for data processing and 15 main palliative care topics across the included studies were identified. The most frequent topic was mortality and prognosis prediction. We also identified a trend where natural language processing was frequently used in analyzing clinical serious illness conversations extracted from audio recordings. CONCLUSIONS: We found 82 papers on palliative care using natural language processing methods for a wide-range of topics and sources of data that could expand the use of this methodology. We encourage researchers to consider incorporating this cutting-edge research methodology in future studies to improve published palliative care data.

Atlantic flower-invertebrate interactions: A data set of occurrence and frequency of floral visits.

Encounters between flowers and invertebrates are key events for the functioning of tropical forests. Assessing the structure of networks composed of the interactions between those partners leads to a better understanding of ecosystem functioning and the effects of environmental factors on ecological processes. Gathering such data is, however, costly and time-consuming, especially in the highly diverse tropics. We aimed to provide a comprehensive repository of available flower-invertebrate interaction information for the Atlantic Forest, a South American tropical forest domain. Data were obtained from published works and "gray literature," such as theses and dissertations, as well as self-reports by co-authors. The data set has ~18,000 interaction records forming 482 networks, each containing between one and 1061 interaction links. Each network was sampled for about 200 h or less, with few exceptions. A total of 641 plant genera within 136 different families and 39 orders were reported, with the most abundant and rich families being Asteraceae, Fabaceae, and Rubiaceae. Invertebrates interacting with these plants were all arthropods from 10 orders, 129 families, and 581 genera, comprising 2419 morphotypes (including 988 named species). Hymenoptera was the most abundant and diverse order, with at least six times more records than the second-ranked order (Lepidoptera). The complete data set shows Hymenoptera interacting with all plant orders and also shows Diptera, Lepidoptera, Coleoptera, and Hemiptera to be important nodes. Among plants, Asterales and Fabales had the highest number of interactions. The best sampled environment was forest (~8000 records), followed by pastures and crops. Savanna, grasslands, and urban environments (among others) were also reported, indicating a wide range of approaches dedicated to collecting flower-invertebrate interaction data in the Atlantic Forest domain. Nevertheless, most reported data were from forest understory or lower strata, indicating a knowledge gap about flower-invertebrate interactions at the canopy. Also, access to remote regions remains a limitation, generating sampling bias across the geographical range of the Atlantic Forest. Future studies in these continuous and hard-to-access forested areas will yield important new information regarding the interactions between flowers and invertebrates in the Atlantic Forest. There are no copyright restrictions on the data set. Please cite this data paper if the data are used in publications and teaching events.

O que mudou entre os períodos de pico e de platô durante a primeira onda do SARS-CoV-2? Estudo multicêntrico português em unidades de cuidados intensivos / What changed between the peak and plateau periods of the first COVID-19 pandemic wave? A multicentric Portuguese cohort study in intensive care

RESUMO Objetivo: Analisar e comparar as características de pacientes críticos com a COVID-19, a abordagem clínica e os resultados entre os períodos de pico e de platô na primeira onda pandêmica em Portugal. Métodos: Este foi um estudo de coorte multicêntrico ambispectivo, que incluiu pacientes consecutivos com a forma grave da COVID-19 entre março e agosto de 2020 de 16 unidades de terapia intensiva portuguesas. Definiram-se as semanas 10 - 16 e 17 - 34 como os períodos de pico e platô. Resultados: Incluíram-se 541 pacientes adultos com mediana de idade de 65 [57 - 74] anos, a maioria do sexo masculino (71,2%). Não houve diferenças significativas na mediana de idade (p = 0,3), no Simplified Acute Physiology Score II (40 versus 39; p = 0,8), na pressão parcial de oxigênio/fração inspirada de oxigênio (139 versus 136; p = 0,6), na terapia com antibióticos na admissão (57% versus 64%; p = 0,2) ou na mortalidade aos 28 dias (24,4% versus 22,8%; p = 0,7) entre o período de pico e platô. Durante o período de pico, os pacientes tiveram menos comorbidades (1 [0 - 3] versus 2 [0 - 5]; p = 0,002); fizeram mais uso de vasopressores (47% versus 36%; p < 0,001) e ventilação mecânica invasiva na admissão (58,1% versus 49,2%; p < 0,001), e tiveram mais prescrição de hidroxicloroquina (59% versus 10%; p < 0,001), lopinavir/ritonavir (41% versus 10%; p < 0,001) e posição prona (45% versus 36%; p = 0,04). Entretanto, durante o platô, observou-se maior uso de cânulas nasais de alto fluxo (5% versus 16%; p < 0,001) na admissão, remdesivir (0,3% versus 15%; p < 0,001) e corticosteroides (29% versus 52%; p < 0,001), além de menor tempo de internação na unidade de terapia intensiva (12 versus 8 dias; p < 0,001). Conclusão: Houve mudanças significativas nas comorbidades dos pacientes, nos tratamentos da unidade de terapia intensiva e no tempo de internação entre os períodos de pico e platô na primeira onda da COVID-19.

ABSTRACT Objective: To analyze and compare COVID-19 patient characteristics, clinical management and outcomes between the peak and plateau periods of the first pandemic wave in Portugal. Methods: This was a multicentric ambispective cohort study including consecutive severe COVID-19 patients between March and August 2020 from 16 Portuguese intensive care units. The peak and plateau periods, respectively, weeks 10 - 16 and 17 - 34, were defined. Results: Five hundred forty-one adult patients with a median age of 65 [57 - 74] years, mostly male (71.2%), were included. There were no significant differences in median age (p = 0.3), Simplified Acute Physiology Score II (40 versus 39; p = 0.8), partial arterial oxygen pressure/fraction of inspired oxygen ratio (139 versus 136; p = 0.6), antibiotic therapy (57% versus 64%; p = 0.2) at admission, or 28-day mortality (24.4% versus 22.8%; p = 0.7) between the peak and plateau periods. During the peak period, patients had fewer comorbidities (1 [0 - 3] versus 2 [0 - 5]; p = 0.002) and presented a higher use of vasopressors (47% versus 36%; p < 0.001) and invasive mechanical ventilation (58.1 versus 49.2%; p < 0.001) at admission, prone positioning (45% versus 36%; p = 0.04), and hydroxychloroquine (59% versus 10%; p < 0.001) and lopinavir/ritonavir (41% versus 10%; p < 0.001) prescriptions. However, a greater use of high-flow nasal cannulas (5% versus 16%, p < 0.001) on admission, remdesivir (0.3% versus 15%; p < 0.001) and corticosteroid (29% versus 52%, p < 0.001) therapy, and a shorter ICU length of stay (12 days versus 8, p < 0.001) were observed during the plateau. Conclusion: There were significant changes in patient comorbidities, intensive care unit therapies and length of stay between the peak and plateau periods of the first COVID-19 wave.

Abordagem odontológica ao paciente vítima de lesão causada por projétil de arma de fogo - revisão de literatura / Dental approach to patient victim of injury clausod by firearm projectil - literature review

O Ferimento por Projétil de Arma de Fogo (PAF), também conhecido como trauma balístico é todo e qualquer trauma físico causado por arma de fogo, sendo considerado um problema de saúde pública mundial, devido sua alta prevalência, seu grande impacto psicossocial e o alto custo com tratamento. O objetivo deste estudo é avaliar as diferentes abordagens terapêuticas relacionadas ao ferimento por arma de fogo na área de cirurgia e traumatologia bucomaxilofacial, contribuindo assim para a elaboração de protocolos de atendimento mais eficazes e formulação de políticas públicas mais eficientes. Para isso, foi realizado uma revisão de literatura nas principais bases de dados: Scielo, Medline e Pubmed, no período entre 1998 e 2021, nas línguas inglesa e portuguesa. Observou-se que este tipo de lesão foi mais prevalente em jovens do sexo masculino, os quais geralmente apresentaram fraturas cominutivas em mandíbula, sendo o tratamento cirúrgico o mais indicado. Sendo assim, é de suma importância que todos os profissionais envolvidos no tratamento ao paciente vítima de PAF saibam tratar de forma adequada, para a melhoria da qualidade de vida de todos os envolvidos.

Firearm Projectile Injury (FPI), also known as ballistic trauma, is any physical trauma caused by a firearm considered a worldwide public health problem due to its high prevalence, great psychosocial impact and the high cost of treatment. The aim of this study is to evaluate the different therapeutic approaches related to gunshot wounds in the area of maxillofacial surgery and traumatology, thus contributing to the development of more effective care protocols and the formulation of more efficient public policies. For this, a literature review was carried out in the main databases: Scielo, Medline and Pubmed, in the period between 1998 and 2021, in English and Portuguese. It was observed that this type of injury was more prevalent in young males, who generally presented comminuted fractures in the mandible, with surgical treatment being the most indicated. Therefore, it is of paramount that all professionals involved in the treatment of FAP know how to treat it properly, providing better health outcomes for its victims.

What changed between the peak and plateau periods of the first COVID-19 pandemic wave? A multicentric Portuguese cohort study in intensive care. / O que mudou entre os períodos de pico e de platô durante a primeira onda do SARS-CoV-2? Estudo multicêntrico português em unidades de cuidados intensivos.

OBJECTIVE: To analyze and compare COVID-19 patient characteristics, clinical management and outcomes between the peak and plateau periods of the first pandemic wave in Portugal. METHODS: This was a multicentric ambispective cohort study including consecutive severe COVID-19 patients between March and August 2020 from 16 Portuguese intensive care units. The peak and plateau periods, respectively, weeks 10 - 16 and 17 - 34, were defined. RESULTS: Five hundred forty-one adult patients with a median age of 65 [57 - 74] years, mostly male (71.2%), were included. There were no significant differences in median age (p = 0.3), Simplified Acute Physiology Score II (40 versus 39; p = 0.8), partial arterial oxygen pressure/fraction of inspired oxygen ratio (139 versus 136; p = 0.6), antibiotic therapy (57% versus 64%; p = 0.2) at admission, or 28-day mortality (24.4% versus 22.8%; p = 0.7) between the peak and plateau periods. During the peak period, patients had fewer comorbidities (1 [0 - 3] versus 2 [0 - 5]; p = 0.002) and presented a higher use of vasopressors (47% versus 36%; p < 0.001) and invasive mechanical ventilation (58.1 versus 49.2%; p < 0.001) at admission, prone positioning (45% versus 36%; p = 0.04), and hydroxychloroquine (59% versus 10%; p < 0.001) and lopinavir/ritonavir (41% versus 10%; p < 0.001) prescriptions. However, a greater use of high-flow nasal cannulas (5% versus 16%, p < 0.001) on admission, remdesivir (0.3% versus 15%; p < 0.001) and corticosteroid (29% versus 52%, p < 0.001) therapy, and a shorter ICU length of stay (12 days versus 8, p < 0.001) were observed during the plateau. CONCLUSION: There were significant changes in patient comorbidities, intensive care unit therapies and length of stay between the peak and plateau periods of the first COVID-19 wave.

OBJETIVO: Analisar e comparar as características de pacientes críticos com a COVID-19, a abordagem clínica e os resultados entre os períodos de pico e de platô na primeira onda pandêmica em Portugal. MÉTODOS: Este foi um estudo de coorte multicêntrico ambispectivo, que incluiu pacientes consecutivos com a forma grave da COVID-19 entre março e agosto de 2020 de 16 unidades de terapia intensiva portuguesas. Definiram-se as semanas 10 - 16 e 17 - 34 como os períodos de pico e platô. RESULTADOS: Incluíram-se 541 pacientes adultos com mediana de idade de 65 [57 - 74] anos, a maioria do sexo masculino (71,2%). Não houve diferenças significativas na mediana de idade (p = 0,3), no Simplified Acute Physiology Score II (40 versus 39; p = 0,8), na pressão parcial de oxigênio/fração inspirada de oxigênio (139 versus 136; p = 0,6), na terapia com antibióticos na admissão (57% versus 64%; p = 0,2) ou na mortalidade aos 28 dias (24,4% versus 22,8%; p = 0,7) entre o período de pico e platô. Durante o período de pico, os pacientes tiveram menos comorbidades (1 [0 - 3] versus 2 [0 - 5]; p = 0,002); fizeram mais uso de vasopressores (47% versus 36%; p < 0,001) e ventilação mecânica invasiva na admissão (58,1% versus 49,2%; p < 0,001), e tiveram mais prescrição de hidroxicloroquina (59% versus 10%; p < 0,001), lopinavir/ritonavir (41% versus 10%; p < 0,001) e posição prona (45% versus 36%; p = 0,04). Entretanto, durante o platô, observou-se maior uso de cânulas nasais de alto fluxo (5% versus 16%; p < 0,001) na admissão, remdesivir (0,3% versus 15%; p < 0,001) e corticosteroides (29% versus 52%; p < 0,001), além de menor tempo de internação na unidade de terapia intensiva (12 versus 8 dias; p < 0,001). CONCLUSÃO: Houve mudanças significativas nas comorbidades dos pacientes, nos tratamentos da unidade de terapia intensiva e no tempo de internação entre os períodos de pico e platô na primeira onda da COVID-19.

Inverted Nasal Papilloma Affecting Ears and Pulmonary Parenchyma: Case Report.

Inverted papilloma is a rare sinonasal neoplasm. It can be locally invasive and potentially degenerate to a malignant tumor. We present a case report of a 36-year-old woman who was treated for nasal inverted papilloma for over 10 years and presented bilateral temporal bone, and pulmonary involvement. Several procedures were performed to completely remove the tumor. Even without evidence of malignant degeneration, the patient continued battling tumor recurrences. To the best of our knowledge, this report presents the first case of a multicentric inverted papilloma with nasal, bilateral temporal bone, and pulmonary metachronous localization. Laryngoscope, 131:E2640-E2642, 2021.

suPAR na avaliação do prognóstico após permanência na unidade de terapia intensiva: um estudo piloto / suPAR in the assessment of post intensive care unit prognosis: a pilot study

RESUMO Objetivo: Determinar o desempenho da dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel quando da alta da unidade de terapia intensiva para predição da mortalidade após permanência na mesma unidade. Métodos: Durante 24 meses conduziu-se um estudo prospectivo observacional de coorte em uma unidade de terapia intensiva polivalente de oito leitos. Colheram-se os seguintes dados: APACHE II, SOFA, níveis de proteína C-reativa e receptor ativador de plasminogênio tipo uroquinase solúvel, além de contagem de leucócitos no dia da alta da unidade de terapia intensiva, em pacientes que sobreviveram à permanência na unidade de terapia intensiva. Resultados: Durante este período, incluíram-se no estudo 202 pacientes; 29 (18,6%) morreram após alta da unidade de terapia intensiva. Os não sobreviventes eram mais idosos e tinham enfermidades mais graves quando admitidos à unidade de terapia intensiva, com escores de severidade mais elevados, e necessitaram de vasopressores por mais tempo do que os que sobreviveram. As áreas sob a curva Característica de Operação do Receptor para SOFA, APACHE II, proteína C-reativa, contagem de leucócitos e receptor ativador de plasminogênio tipo uroquinase solúvel, no momento da alta da unidade de terapia intensiva, avaliadas como marcadores de prognóstico de morte hospitalar, foram, respectivamente, 0,78 (IC95% 0,70 - 0,86); 0,70 (IC95% 0,61 - 0,79); 0,54 (IC95% 0,42 - 0,65); 0,48 (IC95% 0,36 - 0,58); 0,68 (IC95% 0,58 - 0,78). O SOFA associou-se de forma independente com risco mais elevado de morte no hospital (OR 1,673; IC95% 1,252 - 2,234), assim como para mortalidade após 28 dias (OR 1,861; IC95% 1,856 - 2,555) e mortalidade após 90 dias (OR 1,584; IC95% 1,241 - 2,022). Conclusão: A dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel na alta unidade de terapia intensiva teve um valor prognóstico fraco de mortalidade após a permanência nesta unidade.

ABSTRACT Objective: To determine the performance of soluble urokinase-type plasminogen activator receptor upon intensive care unit discharge to predict post intensive care unit mortality. Methods: A prospective observational cohort study was conducted during a 24-month period in an 8-bed polyvalent intensive care unit. APACHE II, SOFA, C-reactive protein, white cell count and soluble urokinase-type plasminogen activator receptor on the day of intensive care unit discharge were collected from patients who survived intensive care unit admission. Results: Two hundred and two patients were included in this study, 29 patients (18.6%) of whom died after intensive care unit discharge. Nonsurvivors were older and more seriously ill upon intensive care unit admission with higher severity scores, and nonsurvivors required extended use of vasopressors than did survivors. The area under the receiver operating characteristics curves of SOFA, APACHE II, C-reactive protein, white cell count, and soluble urokinase-type plasminogen activator receptor at intensive care unit discharge as prognostic markers of hospital death were 0.78 (95%CI 0.70 - 0.86); 0.70 (95%CI 0.61 - 0.79); 0.54 (95%CI 0.42 - 0.65); 0.48 (95%CI 0.36 - 0.58); and 0.68 (95%CI 0.58 - 0.78), respectively. SOFA was independently associated with a higher risk of in-hospital mortality (OR 1.673; 95%CI 1.252 - 2.234), 28-day mortality (OR 1.861; 95%CI 1.856 - 2.555) and 90-day mortality (OR 1.584; 95%CI 1.241 - 2.022). Conclusion: At intensive care unit discharge, soluble urokinase-type plasminogen activator receptor is a poor predictor of post intensive care unit prognosis.

C-reactive protein and procalcitonin profile in ventilator-associated lower respiratory infections.

PURPOSE: Ventilator-associated tracheobronchitis (VAT) has been suggested as an intermediate process between tracheobronchial colonization and ventilator-associated pneumonia (VAP) in patients receiving mechanical ventilation. The aim of this study was to evaluate the ability of C-reactive protein (CRP) and procalcitonin (PCT) to differentiate between VAT and VAP. METHODS: Pre-planned analysis of the prospective multinational TAVeM database, performed on 2960 patients receiving mechanical ventilation for >48 h, including 689 patients with VA-LRTI. Patients with the diagnosis of VAT or VAP microbiologically documented and with one measurement of CRP and/or PCT on the day of diagnosis were included. RESULTS: Four hundred and four patients (mean age 63 years, 298 men, ICU mortality 40%) were studied, 207 with VAT and 197 with VAP. On the day of infection diagnosis, the median CRP was elevated in both groups but significantly higher in VAP (18 mg/dL vs. 14 mg/dL, p = .001). Median PCT was also significantly higher in VAP (2.1 ng/dL vs. 0.64 ng/d L, p < .001). Both biomarkers could not help distinguish between VAT and VAP. CONCLUSION: Although PCT and CRP presented lower values in VAT as compared to VAP, there was a marked overlap of both biomarkers values in both VA-LRTI not allowing adequate discrimination.

Design, synthesis and pharmacological evaluation of N-benzyl-piperidinyl-aryl-acylhydrazone derivatives as donepezil hybrids: Discovery of novel multi-target anti-alzheimer prototype drug candidates.

A new series of sixteen multifunctional N-benzyl-piperidine-aryl-acylhydrazones hybrid derivatives was synthesized and evaluated for multi-target activities related to Alzheimer's disease (AD). The molecular hybridization approach was based on the combination, in a single molecule, of the pharmacophoric N-benzyl-piperidine subunit of donepezil, the substituted hydroxy-piperidine fragment of the AChE inhibitor LASSBio-767, and an acylhydrazone linker, a privileged structure present in a number of synthetic aryl- and aryl-acylhydrazone derivatives with significant AChE and anti-inflammatory activities. Among them, compounds 4c, 4d, 4g and 4j presented the best AChE inhibitory activities, but only compounds 4c and 4g exhibited concurrent anti-inflammatory activity in vitro and in vivo, against amyloid beta oligomer (AßO) induced neuroinflammation. Compound 4c also showed the best in vitro and in vivo neuroprotective effects against AßO-induced neurodegeneration. In addition, compound 4c showed a similar binding mode to donepezil in both acetylated and free forms of AChE enzyme in molecular docking studies and did not show relevant toxic effects on in vitro and in vivo assays, with good predicted ADME parameters in silico. Overall, all these results highlighted compound 4c as a promising and innovative multi-target drug prototype candidate for AD treatment.

suPAR in the assessment of post intensive care unit prognosis: a pilot study. / suPAR na avaliação do prognóstico após permanência na unidade de terapia intensiva: um estudo piloto.

OBJECTIVE: To determine the performance of soluble urokinase-type plasminogen activator receptor upon intensive care unit discharge to predict post intensive care unit mortality. METHODS: A prospective observational cohort study was conducted during a 24-month period in an 8-bed polyvalent intensive care unit. APACHE II, SOFA, C-reactive protein, white cell count and soluble urokinase-type plasminogen activator receptor on the day of intensive care unit discharge were collected from patients who survived intensive care unit admission. RESULTS: Two hundred and two patients were included in this study, 29 patients (18.6%) of whom died after intensive care unit discharge. Nonsurvivors were older and more seriously ill upon intensive care unit admission with higher severity scores, and nonsurvivors required extended use of vasopressors than did survivors. The area under the receiver operating characteristics curves of SOFA, APACHE II, C-reactive protein, white cell count, and soluble urokinase-type plasminogen activator receptor at intensive care unit discharge as prognostic markers of hospital death were 0.78 (95%CI 0.70 - 0.86); 0.70 (95%CI 0.61 - 0.79); 0.54 (95%CI 0.42 - 0.65); 0.48 (95%CI 0.36 - 0.58); and 0.68 (95%CI 0.58 - 0.78), respectively. SOFA was independently associated with a higher risk of in-hospital mortality (OR 1.673; 95%CI 1.252 - 2.234), 28-day mortality (OR 1.861; 95%CI 1.856 - 2.555) and 90-day mortality (OR 1.584; 95%CI 1.241 - 2.022). CONCLUSION: At intensive care unit discharge, soluble urokinase-type plasminogen activator receptor is a poor predictor of post intensive care unit prognosis.

OBJETIVO: Determinar o desempenho da dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel quando da alta da unidade de terapia intensiva para predição da mortalidade após permanência na mesma unidade. MÉTODOS: Durante 24 meses conduziu-se um estudo prospectivo observacional de coorte em uma unidade de terapia intensiva polivalente de oito leitos. Colheram-se os seguintes dados: APACHE II, SOFA, níveis de proteína C-reativa e receptor ativador de plasminogênio tipo uroquinase solúvel, além de contagem de leucócitos no dia da alta da unidade de terapia intensiva, em pacientes que sobreviveram à permanência na unidade de terapia intensiva. RESULTADOS: Durante este período, incluíram-se no estudo 202 pacientes; 29 (18,6%) morreram após alta da unidade de terapia intensiva. Os não sobreviventes eram mais idosos e tinham enfermidades mais graves quando admitidos à unidade de terapia intensiva, com escores de severidade mais elevados, e necessitaram de vasopressores por mais tempo do que os que sobreviveram. As áreas sob a curva Característica de Operação do Receptor para SOFA, APACHE II, proteína C-reativa, contagem de leucócitos e receptor ativador de plasminogênio tipo uroquinase solúvel, no momento da alta da unidade de terapia intensiva, avaliadas como marcadores de prognóstico de morte hospitalar, foram, respectivamente, 0,78 (IC95% 0,70 - 0,86); 0,70 (IC95% 0,61 - 0,79); 0,54 (IC95% 0,42 - 0,65); 0,48 (IC95% 0,36 - 0,58); 0,68 (IC95% 0,58 - 0,78). O SOFA associou-se de forma independente com risco mais elevado de morte no hospital (OR 1,673; IC95% 1,252 - 2,234), assim como para mortalidade após 28 dias (OR 1,861; IC95% 1,856 - 2,555) e mortalidade após 90 dias (OR 1,584; IC95% 1,241 - 2,022). CONCLUSÃO: A dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel na alta unidade de terapia intensiva teve um valor prognóstico fraco de mortalidade após a permanência nesta unidade.

Non-aneurysmal spontaneous subarachnoid hemorrhage: perimesencephalic versus non-perimesencephalic. / Hemorragia subaracnóidea espontânea não aneurismática: perimesencefálica versus não perimesencefálica.

OBJECTIVE: To compare the clinical evolution of perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage. METHODS: The study was conducted retrospectively in a tertiary hospital center in the north region of Portugal. Included patients had no identifiable cause for subarachnoid hemorrhage. Several epidemiologic, clinical and imaging aspects were statistically analyzed, taking into account the differences in perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage. RESULTS: Sixty-two patients met the inclusion criteria (46.8% - perimesencephalic subarachnoid hemorrhage; 53.2% - non-perimesencephalic subarachnoid hemorrhage). Demographic and clinical background characteristics were similar in both groups. Complications were more frequent in patients with non-perimesencephalic subarachnoid hemorrhage - 84.8% of the patients had at least one complication versus 48.3% in perimesencephalic subarachnoid hemorrhage. Vasospasm, infection and hydrocephaly were the most common complications (each was detected more frequently in the non-perimesencephalic subarachnoid hemorrhage group than in perimesencephalic subarachnoid hemorrhage group). Two patients died, both had a non-perimesencephalic subarachnoid hemorrhage. The median inpatient time was longer in the non-perimesencephalic subarachnoid hemorrhage group (21 versus 14 days). No incidents of rebleeding were reported during the follow-up period (mean time of 15 ± 10.3 months). CONCLUSION: Perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage are two different entities that have different clinical outcomes, namely in terms of complication rate and median inpatient time. The management of these patients should respect this difference to improve treatment and optimize health care resources.

Hemorragia subaracnóidea espontânea não aneurismática: perimesencefálica versus não perimesencefálica / Non-aneurysmal spontaneous subarachnoid hemorrhage: perimesencephalic versus non-perimesencephalic

RESUMO Objetivo: Comparar a evolução clínica da hemorragia subaracnóidea perimesencefálica com a da hemorragia subaracnóidea não perimesencefálica. Métodos: Estudo retrospectivo, que incluiu pacientes portadores de hemorragia subaracnóidea sem causa conhecida em um hospital terciário localizado na região norte de Portugal. Os dados epidemiológicos, clínicos e de imagem foram analisados estatisticamente, levando em conta a divisão dos pacientes em duas categorias: hemorragia subaracnóidea perimesencefálica e hemorragia subaracnóidea não perimesencefálica. Resultados: Cumpriram os critérios de inclusão 62 pacientes, 46,8% deles com hemorragia subaracnóidea perimesencefálica e 53,2% com hemorragia subaracnóidea não perimesencefálica. As caraterísticas demográficas, assim como os antecedentes clínicos, foram similares entre os grupos. As complicações foram observadas mais comumente no grupo com hemorragia subaracnóidea não perimesencefálica, sendo que 84,8% desses pacientes tiveram, no mínimo, uma complicação, comparados a 48,3% dos pacientes com hemorragia subaracnóidea perimesencefálica. Vasoespasmo, infecções e hidrocefalia foram as complicações mais comuns - todas observadas mais frequentemente nos pacientes com hemorragia subaracnóidea não perimesencefálica. Dois pacientes vieram a falecer, ambos com hemorragia subaracnóidea não perimesencefálica. A mediana do tempo de permanência no hospital foi maior nos pacientes com hemorragia subaracnóidea não perimesencefálica (21 dias, em comparação aos 14 dias observados nos pacientes com hemorragia subaracnóidea perimesencefálica). Não se observaram recidivas de sangramento durante o acompanhamento (tempo médio de 15 ± 10,3 meses). Conclusão: As hemorragias subaracnóideas perimesencefálica e não perimesencefálica tiveram formas diferentes de evolução clínica, principalmente no que se referiu à taxa de complicações e ao tempo mediano de permanência no hospital. Assim, a abordagem dessas duas formas de hemorragia subaracnóidea deve ser distinta, tanto em busca de melhorar o tratamento dos pacientes quanto para obter um melhor aproveitamento dos recursos de saúde.

ABSTRACT Objective: To compare the clinical evolution of perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage. Methods: The study was conducted retrospectively in a tertiary hospital center in the north region of Portugal. Included patients had no identifiable cause for subarachnoid hemorrhage. Several epidemiologic, clinical and imaging aspects were statistically analyzed, taking into account the differences in perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage. Results: Sixty-two patients met the inclusion criteria (46.8% - perimesencephalic subarachnoid hemorrhage; 53.2% - non-perimesencephalic subarachnoid hemorrhage). Demographic and clinical background characteristics were similar in both groups. Complications were more frequent in patients with non-perimesencephalic subarachnoid hemorrhage - 84.8% of the patients had at least one complication versus 48.3% in perimesencephalic subarachnoid hemorrhage. Vasospasm, infection and hydrocephaly were the most common complications (each was detected more frequently in the non-perimesencephalic subarachnoid hemorrhage group than in perimesencephalic subarachnoid hemorrhage group). Two patients died, both had a non-perimesencephalic subarachnoid hemorrhage. The median inpatient time was longer in the non-perimesencephalic subarachnoid hemorrhage group (21 versus 14 days). No incidents of rebleeding were reported during the follow-up period (mean time of 15 ± 10.3 months). Conclusion: Perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage are two different entities that have different clinical outcomes, namely in terms of complication rate and median inpatient time. The management of these patients should respect this difference to improve treatment and optimize health care resources.

Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study.

BACKGROUND: Ventilator-associated tracheobronchitis has been suggested as an intermediate process between tracheobronchial colonisation and ventilator-associated pneumonia in patients receiving mechanical ventilation. We aimed to establish the incidence and effect of ventilator-associated tracheobronchitis in a large, international patient cohort. METHODS: We did a multicentre, prospective, observational study in 114 intensive care units (ICU) in Spain, France, Portugal, Brazil, Argentina, Ecuador, Bolivia, and Colombia over a preplanned time of 10 months. All patients older than 18 years admitted to an ICU who received invasive mechanical ventilation for more than 48 h were eligible. We prospectively obtained data for incidence of ventilator-associated lower respiratory tract infections, defined as ventilator-associated tracheobronchitis or ventilator-associated pneumonia. We grouped patients according to the presence or absence of such infections, and obtained data for the effect of appropriate antibiotics on progression of tracheobronchitis to pneumonia. Patients were followed up until death or discharge from hospital. To account for centre effects with a binary outcome, we fitted a generalised estimating equation model with a logit link, exchangeable correlation structure, and non-robust standard errors. This trial is registered with ClinicalTrials.gov, number NCT01791530. FINDINGS: Between Sept 1, 2013, and July 31, 2014, we obtained data for 2960 eligible patients, of whom 689 (23%) developed ventilator-associated lower respiratory tract infections. The incidence of ventilator-associated tracheobronchitis and that of ventilator-associated pneumonia at baseline were similar (320 [11%; 10·2 of 1000 mechanically ventilated days] vs 369 [12%; 8·8 of 1000 mechanically ventilated days], p=0·48). Of the 320 patients with tracheobronchitis, 250 received appropriate antibiotic treatment and 70 received inappropriate antibiotics. 39 patients with tracheobronchitis progressed to pneumonia; however, the use of appropriate antibiotic therapy for tracheobronchitis was associated with significantly lower progression to pneumonia than was inappropriate treatment (19 [8%] of 250 vs 20 [29%] of 70, p<0·0001; crude odds ratio 0·21 [95% CI 0·11-0·41]). Significantly more patients with ventilator-associated pneumonia died (146 [40%] of 369) than those with tracheobronchitis (93 [29%] of 320) or absence of ventilator-associated lower respiratory tract infections (673 [30%] of 2271, p<0·0001). Median time to discharge from the ICU for survivors was significantly longer in the tracheobronchitis (21 days [IQR 15-34]) and pneumonia (22 [13-36]) groups than in the group with no ventilator-associated lower respiratory tract infections (12 [8-20]; hazard ratio 1·65 [95% CI 1·38-1·97], p<0·0001). INTERPRETATION: This large database study emphasises that ventilator-associated tracheobronchitis is a major health problem worldwide, associated with high resources consumption in all countries. Our findings also show improved outcomes with use of appropriate antibiotic treatment for both ventilator-associated tracheobronchitis and ventilator-associated pneumonia, underlining the importance of treating both infections, since inappropriate treatment of tracheobronchitis was associated with a higher risk of progression to pneumonia. FUNDING: None.

Impact of systemic corticosteroids on the clinical course and outcomes of patients with severe community-acquired pneumonia: a cohort study.

INTRODUCTION: Our aim was to evaluate the impact of corticosteroids on clinical course and outcomes of patients with severe community-acquired pneumonia (CAP) requiring invasive mechanical ventilation. METHODS: This was a cohort study of patients with severe CAP from 2 intensive care units in tertiary hospitals in Brazil and Portugal. RESULTS: A total of 111 patients were included (median age, 69 years; 56% men; 34% hospital mortality). Corticosteroids were prescribed in 61 (55%) patients. Main indications for their use were bronchospasm (52.5%) and septic shock (36%). Mortality rate of patients treated with and without corticosteroids was comparable (29.5% vs 32%, P = .837). No significant differences were observed on clinical course from day 1 to day 7 as assessed by the Sequential Organ Failure Assessment score (P = .95). Furthermore, C-reactive protein declined similarly in both groups (P = .147). In a multivariate analysis, mortality was associated with older age and higher Acute Physiology and Chronic Health Evaluation II score. CONCLUSIONS: In patients with severe CAP requiring invasive mechanical ventilation, adjunctive therapy with corticosteroids did not influence intensive care unit and hospital mortality. In addition, no changes were observed on weaning from vasopressors, on recovery from organ failure/dysfunction as assessed by the Sequential Organ Failure Assessment score, as well as on C-reactive protein course.

Influência do método de polimerização na microdureza de compósitos microhíbridos armazenados em água destilada / Influence of curing method on the micro hardness of microhybrid composites immersed in distilled water

O objetivo do presente estudo é comparar e avaliar a microdureza Vickers de um compósito restaurador microhíbrido ativado por dois tipos de unidades polimerizadoras e armazenados em água destilada. Trinta espécimes foram feitos com resina Charisma B1, para cada um dos regimes de polimerização: fotopolimerização por luz halógena, fotopolimerização por LED e fotopolimerização mais ciclo adicional em autoclave. Foram feitas duas leituras de microdureza Vickers por corpo de prova em 1 dia, 7 dias e 14 dias de imersões. O ciclo adicional de polimerização mostrou uma tendência de aumentar os valores de microdureza dos compósitos restauradores, não mostrando diferenças estatisticamente significantes entre LED e Luz Halógena (p > 0,05).

The purpose of this study is to evaluate and compare the Vickers microhardness of one microhybrid composite polymerized with different sources and stored in distilled water for up to 14 days. Thirty samples have been prepared with Charisma composite, shade B1, for each polymerization method: halogen light photopolymerization, LED photopolymerization, photopolymerization plus post-cured cycles in autoclave. Two readings of Vichers micro hardness have been done in each sample on 24h, 7days and 14 days of storage. The post curing method tended to improve the microhardness, but it was not statistically different from halogen or LED curing methods (p > 0.05). After 7 days, the hardness values were higher than the first day, but statistically not different to 14 days (p < 0.05). Post-cured samples in autoclave had an improved mean value, however, without differing from those of the LED and halogen.

Fraturas diafisárias de fêmur em crianças e adolescentes / Femoral shaft fractures in children and adolescents

Foram avaliados 71 pacientes com idade abaixo de 16 anos, portadores de 72 fraturas diafisárias do fêmur, ocorridas de 01/1995 a 12/1998. Os objetivos do estudo foram conhecer aspectos descritivos dessas fraturas e avaliar o tratamento empregado. A idade foi o principal critério para escolha do tratamento, sendo aqueles abaixo de 3 anos (Grupo I) tratados com gesso imediato, os de 3 a 10 anos (Grupo II) com gesso após tração e os acima de 11 anos (Grupo III) de modo conservador ou cirúrgico. A média de idade foi 6,3±3,8 anos, havendo predomínio do gênero masculino e de fraturas fechadas. Acidente de trânsito foi o mecanismo de lesão mais comum. A fratura localizou-se no terço médio, em 60,6 por cento dos casos, no proximal em 23,9 por cento e no distal em 15,5 por cento. Noventa e três porcento eram fraturas de traço simples, 4,2 por cento cominutivas e 2,8 por cento segmentares. Lesões associadas foram identificadas em 35,2 por cento dos pacientes. Todas fraturas nos Grupos I e II e 60 por cento daquelas no Grupo III foram tratadas conservadoramente. As complicações observadas até a união óssea foram: discrepância, infecção no trajeto do fio, consolidação viciosa e limitação de movimento do joelho. O tempo médio de consolidação foi 8,6±3,4 semanas, variando com a idade. Concluiu-se que as características das fraturas estudadas foram semelhantes às citadas na literatura e que o tratamento empregado apresentou bom resultado.

Seventy one patients below the age of 16, with 72 shaft femur fractures occurred between January 1995 and December 1998, were evaluated. The purpose of the study was to understand the descriptive aspects of the fractures and appraise the employed treatment. Age was the key criterion for treatment choice, with those under 3 years old (Group I) being treated with immediate spica cast; those between 3 and 10 years (Group II) were treated with traction followed by spica cast, and those over 11 years old (Group III) with conservative or surgical therapy. Mean age was 6.3±3.8 years with a prevalence of males and closed fractures. Traffic accident was the most common injury cause. The fracture was in the middle third in 60.6 percent of the cases, in the proximal third in 23.9 percent, and in the distal third in 15.5 percent. Ninety three percent were simple trace fractures, 4.2 percent comminutive and 2.8 percent segmental. Associated injuries were identified in 35.2 percent of the patients. All fractures in Groups I, II and 60.0 percent of those in group III were treated conservatively. Complications seen until bone union were: discrepancy, infection at the wire path, vicious union and limited knee motion. The average time for union was 8.6±3.4 weeks, varying with age. We conclude that the studied fractures' characteristics were similar to those described by current literature and that the employed treatment showed good outcomes.

Influência do nível protéico e/ou da acidificaçäo da dieta sobre a diarréia pós-desmame em leitöes causada por Escherichia coli / Effect of pigs diet protein level and/or accidification in the Escherichia coli post-weaning diarrhea

Estudou-se experimentalmente a possibilidade de se prevenir a diarréia pós-desmama por Escherichia coli através da reduçäo da proteína e/ou acidificaçäo da dieta. Utilizaram-se 16 leitöes Landrace SPF (Specific Pathogen Free) com 35 dias de idade (dia da desmama), distribuídos em quatro tratamentos (T): TA - raçäo controle com 20% de PB; TB - raçäo do TA com 2% de ácido cítrico; TC - raçäo com 16% PB mais lisina até nível de 0,9%; TD - raçäo do TC mais 2% do ácido cítrico. As raçöes foram formuladas com milho, farelo de soja, minerais e vitaminas. Os leitöes receberam as dietas experimentais do DO (dia da desmama) até D10 (dia do sacrifício). Todos os leitöes foram inoculados com 20 ml de um cultivo de E. coli 0141 K85 contendo 109 UFC/ml, nos dias D3 e D4. Os parâmetros analisados foram: ocorrência de diarréia, eliminaçäo nas fezes e colonizaçäo intestinal da amostra de E. coli inoculada, pH do conteúdo gastrointestinal e histologia do intestino delgado. Tanto a adiçäo do ácido cítrico (TB) como a reduçäo da PB (TC) na dieta tiveram efeito benéfico na ocorrência da diarréia por E. coli. Este efeito mostrou-se mais evidente com a reduçäo da PB e adiçäo do ácido simultaneamente (TD). A diarréia foi prevenida, possivelmente pela reduçäo do pH do estômago e jejuno e por evitar a multiplicaçäo exagerada de E. coli no conteúdo intestinal