Several serological tests have been used successfully in the diagnosis of paracoccidioidomycosis (PCM). In contrast, data about the use of these tests in the follow-up of PCM patients have been heterogeneous. In this study, serum samples from 43 PCM patients with different clinical forms were analysed by counter-immuno-electrophoresis (CIE), complement fixation (CF) and ELISA before treatment. With CIE and ELISA, the chronic unifocal form showed significantly lower antibody levels compared with chronic multifocal and acute forms. Acute form patients had significantly higher titres than patients with multifocal disease by CIE but not by ELISA. No significant differences were observed with CF. Twenty-seven of these patients were followed-up for 2 years and showed a decline in antibody levels by all three tests, paralleling clinical improvement. However, only patients with unifocal disease cleared their antibodies after 1 year of treatment as analysed by CF and ELISA and after 2 years by CIE, suggesting that these patients may need shorter courses of therapy. Patients with the other clinical form of the disease needed > or =2 years of therapy to clear their antibodies. Sera from a further five patients who presented with a relapse were analysed. At the time of relapse all showed increases in antibody levels by CIE and ELISA, but only three showed increases by CF tests. Therefore, CIE and ELISA demonstrated a better clinical correlation than CF, probably reflecting the fungal burden of PCM patients more accurately.

Background: We hypothesized that one single episode of acute kidney injury (AKI) reduces long-term survival compared with no acute kidney injury (No AKI) following recovery from critical illness. Materials and methods: A prospective cohort of 2,010 patients admitted to the ICU between 2000 and 2009 at a provincial referral hospital was followed to determine whether AKI influences long-term survival. Results: Of the 1,844 eligible patients, 18.4% had AKI stage 1, 12.1% had stage 2, 26.5% had stage 3, and 43.0% had No AKI, using the KDIGO classification. The mean and median follow-up time was 8.1 and 8.7 years. The 28-day, 1-year, 5-year and 10-year survival rates were 59.6%, 44.9%, 37.4%, and 33.4%, in patients with any AKI (stage 1, stage 2, stage 3), which was significantly worse compared with the critically ill patients with no AKI at any time (P < 0.01). The adjusted 10-year mortality risk associated with AKI was 1.44 (95% CI = 1.2 to 1.7) among 28-day survivors. Patients who had mild AKI (stage 1) had significantly worse survival at 28 days, 1 year, 3 years, 5 years and 10 years compared with No AKI (P < 0.01) (Figure 1A). Patients with sepsis and AKI who survived 28 days had significantly poorer 5-year and 10-year survival compared with nonseptic AKI (P < 0.01) (Figure 1B). Conclusions: Patients with one episode of mild (stage 1) AKI have significantly lower survival rates over 10 years than critically ill patients without AKI. The causes and mechanisms of this association warrant further careful study. Close medical follow-up of these patients may be warranted and mechanistic research required understanding how AKI influences distant events.

Background Appropriate use of antimicrobials is essential to improve outcomes in sepsis. The aim of this study was to determine whether the use of a rapid molecular blood test—Septi Fast (SF) reduces the antibiotic consumption through early de-escalation in patients with nosocomial sepsis compared with conventional blood cultures (BCs). Methods This was a prospective, randomized, superiority, controlled trial conducted at Sao Paulo Heart Institute in the period October 2012–May 2016. Adult patients admitted to the hospital for at least 48 h with a diagnosis of nosocomial sepsis underwent microorganism identification by both SF test and BCs. Patients randomized into the intervention group received antibiotic therapy adjustment according to the results of SF. Patients randomized into the control group received standard antibiotic adjustment according to the results of BCs. The primary endpoint was antimicrobial consumption during the first 14 days after randomization. Results A total of 200 patients were included (100 in each group). The intention to treat analysis found no significant differences in median antibiotic consumption. In the subgroup of patients with positive SF and blood cultures (19 and 25 respectively), we found a statistically significant reduction in the median antimicrobial consumption which was 1429 (1071–2000) days of therapy (DOT)/1000 patients-day in the intervention group and 1889 (1357–2563) DOT/1000 patients-day in the control group ( p = 0.017), in the median time of antimicrobial de-escalation (8 versus 54 h— p < 0.001), in the duration of antimicrobial therapy ( p = 0.039) and in anti-gram-positive antimicrobial costs ( p = 0.002). Microorganism identification was possible in 24.5% of patients (45/184) by SF and 21.2% (39/184) by BC ( p = 0.45). Conclusion This randomized clinical trial showed that the use of a rapid molecular-based pathogen identification test does not reduce the median antibiotic consumption in nosocomial sepsis. However, in patients with positive microbiological tests, the use of Septi Fast reduced antimicrobial consumption through early de-escalation compared to conventional blood cultures. These results were driven by a reduction in the consumption of antimicrobials used for Gram-positive bacteria. Trial registration The trial was registered at ClinicalTrials.gov ( NCT 01450358 ) on 12th October 2011 Electronic supplementary material The online version of this article (10.1186/s40560-019-0391-3) contains supplementary material, which is available to authorized users.

Previous studies have examined the arrangement of regulatory elements along the apolipoprotein B (apoB) promoter region (-3067 to +940) and a promoter fragment extending from nucleotides -150 to +124 has been demonstrated to be essential for transcriptional activation of the apoB gene in hepatic and intestinal cells. It has also been shown that transcriptional activation of apoB requires a synergistic interaction between hepatic nuclear factor-4 (HNF-4) and CCAAT/ enhancer-binding protein α (C/EBPα) transcription factors. Here, we have examined the hypothesis that HNF-4 factor binding to DNA may induce a DNA helix bend, thus facilitating the communication with a C/EBPα factor located one helix turn from this HNF-4 factor in the apoB promoter. A gel electrophoretic mobility shift assay using wild type double-stranded oligonucleotides or modified wild type duplex oligonucleotides with 10 nucleotides inserted between HNF-4 and C/ EBPα factor motifs showed similar retarded complexes, indicating that HNF-4 and C/EBPα factors interact independently of the distance between binding sites. However, when only one base, a thymidine, was inserted at the -71 position of the apoB promoter, the complex shift was completely abolished. In conclusion, these results regarding the study of the mechanisms involving the interaction between HNF-4 and C/EBPα factors in the apoB promoter suggest that the perfect 5'-CCCTTTGGA-3' motif is needed in order to facilitate the interaction between the two factors.

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