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Acute-phase protein (APPs) serum levels have been studied in many human diseases, and their components contribute to host defense during the evolution of infectious diseases by acting as part of the innate immune system. Based on the importance of establishing new experimental models, the present investigation evaluated the modulation of APPs following inflammatory stimulus by the inoculation of Aeromonas hydrophila in tilapias. Fish were sampled 6 and 24 hours post-infection. Tilapias presented increase of positive APPs such as ceruloplasmin, haptoglobin, alpha-2-macroglobulin and complement C3, as well as decrease of negative APPs such as albumin and transferrin. The protein response of tilapias during the course of bacterial infection showed correlation with the kinetics of cellular accumulation in the inflamed focus with significant increase of granulocytes, thrombocytes, lymphocytes and macrophages. However, granulocytes were the predominant cells, associated with increment in the reactive oxygen species (ROS) production. Showing responses similar to those observed in humans, the modulation of APPs and the kinetics of cellular accumulation in the exudate demonstrate the feasibility of this alternative experimental model for advances and studies to understand changes in pathophysiological mechanisms of acute inflammatory reaction due to bacterial infection.

The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19. We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278. 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94–1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups. In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19. COALITION COVID-19 Brazil and EMS.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2015 and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/annualupdate2015 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

Readmission to the intensive care unit (ICU) is associated with poor clinical outcomes, increased length of ICU and hospital stay, and higher costs. Nevertheless, knowledge of epidemiology of ICU readmissions, risk factors, and attributable outcomes is restricted to developed countries. To determine the effect of ICU readmissions on in-hospital mortality, determine incidence of ICU readmissions, identify predictors of ICU readmissions and hospital mortality, and compare resource use and outcomes between readmitted and nonreadmitted patients in a developing country. This retrospective single-center cohort study was conducted in a 40-bed, open medical-surgical ICU of a private, tertiary care hospital in São Paulo, Brazil. The Local Ethics Committee at Hospital Israelita Albert Einstein approved the study protocol, and the need for informed consent was waived. All consecutive adult (≥18 yr) patients admitted to the ICU between June 1, 2013 and July 1, 2015 were enrolled in this study. Comparisons were made between patients readmitted and not readmitted to the ICU. Logistic regression analyses were performed to identify predictors of ICU readmissions and hospital mortality. Out of 5,779 patients admitted to the ICU, 576 (10%) were readmitted to the ICU during the same hospitalization. Compared with nonreadmitted patients, patients readmitted to the ICU were more often men (349 of 576 patients [60.6%] vs. 2,919 of 5,203 patients [56.1%]; P = 0.042), showed a higher (median [interquartile range]) severity of illness (Simplified Acute Physiology III score) at index ICU admission (50 [41-61] vs. 42 [32-54], respectively, for readmitted and nonreadmitted patients; P < 0.001), and were more frequently admitted due to medical reasons (425 of 576 [73.8%] vs. 2,998 of 5,203 [57.6%], respectively, for readmitted and nonreadmitted patients; P < 0.001). Simplified Acute Physiology III score (P < 0.001), ICU admission from the ward (odds ratio [OR], 1.907; 95% confidence interval [CI], 1.463-2.487; P < 0.001), vasopressors need during index ICU stay (OR, 1.391; 95% CI, 1.130-1.713; P = 0.002), and length of ICU stay (P = 0.001) were independent predictors of ICU readmission. After adjusting for severity of illness, ICU readmission (OR, 4.103; 95% CI, 3.226-5.518; P < 0.001), admission source, presence of cancer, use of vasopressors, mechanical ventilation or renal replacement therapy, length of ICU stay, and nighttime ICU discharge were associated with increased risk of in-hospital death. Readmissions to the ICU were frequent and strongly related to poor outcomes. The degree to which ICU readmissions are preventable as well as the main causes of preventable ICU readmissions need to be further determined.

Mobilization of critically ill patients is safe and may improve functional outcomes. However, the prevalence of mobilization activities of ICU patients in Brazil is unknown. A one-day point prevalence prospective study with a 24-hour follow-up period was conducted in Brazil. Demographic data, ICU characteristics, prevalence of mobilization activities, level of patients' mobilization, and main reasons for not mobilizing patients were collected for all adult patients with more than 24hs of ICU stay in the 26 participating ICUs. Mobilization activity was defined as any exercise performed during ICU stay. In total, 358 patients were included in this study. Mobilization activities were performed in 87.4% of patients. Patients received mobilization activities while under invasive mechanical ventilation (44.1%), noninvasive ventilation (11.7%), or without any ventilatory support (44.2%). Passive exercises were more frequently performed [46.5% in all patients; 82.3% in mechanically ventilated patients]. Mobilization activities included in-bed exercise regimen (72.2%). Out-of-bed mobility was reported in 39.9% of mobilized patients, and in 16.3% of patients under invasive mechanical ventilation. The presence of an institutional early mobility protocol was associated with early mobilization (OR, 3.19; 95% CI, 1.23 to 8.22; p = 0.016), and with out-of-bed exercise (OR, 5.80; 95% CI, 1.33 to 25.30; p = 0.02). Mobilization activities in critically ill patients in Brazil was highly prevalent, although there was almost no active mobilization in the mechanically ventilated patients. Moreover, the presence of an institutional early mobility protocol was associated with a threefold higher chance of ICU mobilization during that day.

Bones are among the structures most likely to be recovered after death. However, the low quantity of preserved DNA and complex processing from sample to DNA profile make forensic DNA analysis of bones a challenging task. Raman spectroscopy and gas chromatography-mass spectrometry (GC/MS), have the potential to be useful as screening tools for DNA analysis and in decomposition studies. The objective of this research was to assess the usefulness of such molecular investigations. Femur samples collected from 50 decomposing human bodies were subjected to Raman spectroscopy and GC/MS. Assessment of nuclear DNA quantity and short tandem repeat (STR) genotyping efficiency were also performed. Raman parameters (crystallinity, carbonate-to-phosphate ratio, mineral-to-matrix ratio) and detected lipids were recorded. Background fluorescence proved problematic for Raman analysis of forensic bones. Regardless, it was not associated with less preserved DNA or less detected STR alleles. Fatty acids, hydrocarbons, and five types of fatty acid methyl esters (FAMEs) were detected. The main phosphate peak position in Raman spectra was significantly correlated with preserved DNA (p = 0.03713), while significantly more STR alleles were detected in bones containing methyl hexadecenoate (p = 0.04236). Detection of FAMEs in the bone matrix suggests a reaction between methanol produced by bacteria and free fatty acids, which are not associated with the level of preservation of endogenous DNA. The techniques assessed have shown to be useful in molecular taphonomy studies and forensic genetics. •Raman spectroscopy and gas chromatography-mass spectrometry, are useful in decomposition studies.•the main phosphate peak position in Raman spectra was significantly correlated with preserved DNA.•significantly more STR alleles were detected in bones containing methyl hexadecenoate.•bacterial methanol and free fatty acids form esters during decomposition.•Raman analysis of forensic bones can be hampered by background fluorescence.

Cases of Alzheimer’s disease (AD) are rising exponentially due to increasing global life expectancy. There are approximately 50 million sufferers worldwide, with prevalence rising most rapidly in low-income countries such as Africa and Asia. There is currently no definite diagnosis of AD until after death, thus an early biomarker for AD is urgently required in order to administer timelier and more effective interventions. Olfactory dysfunction (problems with the sense of smell) is one of the earliest, preclinical symptoms observed in AD. Olfaction is a promising early biomarker for use worldwide as it is easy, cheap to measure, and not reliant on specialist clinicians or laboratory analysis. We carried out a meta-analysis to determine the credibility of olfaction in diagnosing AD in the preclinical stages, by comparing olfaction in healthy controls against AD patients and patients with mild cognitive impairment (MCI). Data from 10 articles were subjected to two comparative meta-analyses. In the case of AD, the results illustrated that the overall magnitude of effect size was more apparent, d = −1.63, 95% CI [−1.95, −1.31], in comparison to that of MCI, d = −0.81, 95% CI [−1.08, −0.55]. This shows that olfaction worsens progressively as patients progress from MCI to AD, highlighting the potential for olfactory dysfunction to identify AD in the preclinical stages prior to MCI.

PurposeFrail patients are known to experience poor outcomes. Nevertheless, we know less about how frailty manifests itself in patients’ physiology during critical illness and how it affects resource use in intensive care units (ICU). We aimed to assess the association of frailty with short-term outcomes and organ support used by critically ill patients.MethodsRetrospective analysis of prospective collected data from 93 ICUs in Brazil from 2014 to 2015. We assessed frailty using the modified frailty index (MFI). The primary outcome was in-hospital mortality. Secondary outcomes were discharge home without need for nursing care, ICU and hospital length of stay (LOS), and utilization of ICU organ support and transfusion. We used mixed logistic regression and competing risk models accounting for relevant confounders in outcome analyses.ResultsThe analysis consisted of 129,680 eligible patients. There were 40,779 (31.4%) non-frail (MFI = 0), 64,407 (49.7%) pre-frail (MFI = 1–2) and 24,494 (18.9%) frail (MFI ≥ 3) patients. After adjusted analysis, frailty was associated with higher in-hospital mortality (OR 2.42, 95% CI 1.89–3.08), particularly in patients admitted with lower SOFA scores. Frail patients were less likely to be discharged home (OR 0.36, 95% CI 0.54–0.79) and had higher hospital and ICU LOS than non-frail patients. Use of all forms of organ support (mechanical ventilation, non-invasive ventilation, vasopressors, dialysis and transfusions) were more common in frail patients and increased as MFI increased.ConclusionsFrailty, as assessed by MFI, was associated with several patient-centered endpoints including not only survival, but also ICU LOS and organ support.

PurposeTo study whether ICU staffing features are associated with improved hospital mortality, ICU length of stay (LOS) and duration of mechanical ventilation (MV) using cluster analysis directed by machine learning.MethodsThe following variables were included in the analysis: average bed to nurse, physiotherapist and physician ratios, presence of 24/7 board-certified intensivists and dedicated pharmacists in the ICU, and nurse and physiotherapist autonomy scores. Clusters were defined using the partition around medoids method. We assessed the association between clusters and hospital mortality using logistic regression and with ICU LOS and MV duration using competing risk regression.ResultsAnalysis included data from 129,680 patients admitted to 93 ICUs (2014–2015). Three clusters were identified. The features distinguishing between the clusters were: the presence of board-certified intensivists in the ICU 24/7 (present in Cluster 3), dedicated pharmacists (present in Clusters 2 and 3) and the extent of nurse autonomy (which increased from Clusters 1 to 3). The patients in Cluster 3 exhibited the best outcomes, with lower adjusted hospital mortality [odds ratio 0.92 (95% confidence interval (CI), 0.87–0.98)], shorter ICU LOS [subhazard ratio (SHR) for patients surviving to ICU discharge 1.24 (95% CI 1.22–1.26)] and shorter durations of MV [SHR for undergoing extubation 1.61(95% CI 1.54–1.69)]. Cluster 1 had the worst outcomes.ConclusionPatients treated in ICUs combining 24/7 expert intensivist coverage, a dedicated pharmacist and nurses with greater autonomy had the best outcomes. All of these features represent achievable targets that should be considered by policy makers with an interest in promoting equal and optimal ICU care.

Infectious keratoconjunctivitis (IKC) is the most frequent ocular disease in livestock worldwide and is primarily caused by Moraxella bovis, M. ovis, and/or M. bovoculi. The economic impact of IKC is mainly due to ocular damage, which leads to weight loss, management difficulties, pain and discomfort, and cost of treatments. In horses, limited information is available on the association of Moraxella spp. with keratoconjunctivitis. The present report describes two cases of equine keratoconjunctivitis caused by members of the genus Moraxella. Both animals presented with lacrimation, conjunctivitis, photophobia, mucoid or purulent secretions, blepharitis, and conjunctival hyperemia. The diagnosis of IKC was based on the epidemiological and clinical findings; the etiological agent was identified through bacteriological (culture and biochemistry assays) and molecular testing (PCR and nucleotide sequencing). Our study reports the isolation of Moraxella bovoculi (SBP 88/19) and a putative new species/mutant of Moraxella (SBP 39/19) recovered from ocular secretions in horses. Thus, we suggest the inclusion of Moraxella spp. infection in the differential diagnosis of conjunctivitis in horses in Southern Brazil.