Subunit vaccines are a potential intervention strategy against leptospirosis, which is a major public health problem in developing countries and a veterinary disease in livestock and companion animals worldwide. Leptospiral immunoglobulin-like (Lig) proteins are a family of surface-exposed determinants that have Ig-like repeat domains found in virulence factors such as intimin and invasin. We expressed fragments of the repeat domain regions of LigA and LigB from Leptospira interrogans serovar Copenhageni. Immunization of Golden Syrian hamsters with Lig fragments in Freund's adjuvant induced robust antibody responses against recombinant protein and native protein, as detected by ELISA and immunoblot, respectively. A single fragment, LigANI, which corresponds to the six carboxy-terminal Ig-like repeat domains of the LigA molecule, conferred immunoprotection against mortality (67-100%, P<0.05) in hamsters which received a lethal inoculum of L. interrogans serovar Copenhageni. However, immunization with this fragment did not confer sterilizing immunity. These findings indicate that the carboxy-terminal portion of LigA is an immunoprotective domain and may serve as a vaccine candidate for human and veterinary leptospirosis.

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There is an urgent need for improved diagnosis of leptospirosis, an emerging infectious disease which imparts a large disease burden in developing countries. We evaluated the use of Leptospira immunoglobulin (Ig)-like (Lig) proteins as a serodiagnostic marker for leptospirosis. Lig proteins have bacterial immunoglobulin-like (Big) tandem repeat domains, a moiety found in virulence factors in other pathogens. Sera from patients identified during urban outbreaks in Brazil reacted strongly with immunoblots of a recombinant fragment comprised of the second to sixth Big domains of LigB from L. interrogans serovar Copenhageni, the principal agent for transmission in this setting. Furthermore, the sera recognized an analogous LigB fragment derived from L. kirschneri serovar Grippotyphosa, a pathogenic serovar which is not endemic to the study area. The immunoblot assay detected anti-LigB IgM antibodies in sera from 92% (95% confidence interval, 85 to 96%) of patients during acute-phase leptospirosis. The assay had a sensitivity of 81% for sera from patients with less than 7 days of illness. Anti-LigB antibodies were found in sera from 57% of the patients who did not have detectable anti-whole-Leptospira responses as detected by IgM enzyme-linked immunosorbent assay and microagglutination test. The specificities of the assay were 93 to 100% and 90 to 97% among sera from healthy individuals and patients with diseases that have clinical presentations that overlap with those of leptospirosis, respectively. These findings indicate that the antibody response to this putative virulence determinant is a sensitive and specific marker for acute infection.

BackgroundThis study aimed to identify predictors of early (7-day) mortality in patients with septic acute kidney injury (AKI) who required continuous renal replacement therapy (CRRT).MethodsProspective cohort of 186 septic AKI patients undergoing CRRT at a tertiary hospital, from October 2005 to November 2010.ResultsAfter multivariate adjustment, five variables were associated to early mortality: norepinephrine utilization, liver failure, medical condition, lactate level, and pre-dialysis creatinine level. These variables were combined in a score, which demonstrated good discrimination, with a C-statistic of 0.82 (95% CI = 0.76–0.88), and good calibration (χ 2 = 4.3; p = 0.83). SAPS 3, APACHE II and SOFA scores demonstrated poor performance in this population.ConclusionsThe HEpatic failure, LactatE, NorepInephrine, medical Condition, and Creatinine (HELENICC) score outperformed tested generic models. Future studies should further validate this score in different cohorts.

O xidative stress has been implicated as a cause of the endothelial damage seen in preeclampsia. This randomized, placebo-controlled double-blind trial involving 4 Brazilian clinical sites examined whether dietary antioxidant supplementation would reduce the incidence of preeclampsia in patients at increased risk because of the presence chronic hypertension or a history of preeclampsia.Patients were 12 to 19 weeks pregnant at enrollment and were randomly assigned to receive 1000 mg vitamin C and 400 IU vitamin E daily or placebo. Patients took 2 gel capsules containing one-half of each medication daily from enrollment to delivery or the diagnosis of preeclampsia. They were followed at periodic prenatal visits at which time blood pressure, weight, and urinary protein excretion were measured. The primary outcome was the development of preeclampsia (blood pressure of 140/90 mm Hg and 300 mg/24 h urinary protein); secondary outcomes were severity of preeclampsia (severe vs. not severe using usual internationally agreed upon criteria), gestational hypertension, abruptio placentae, premature rupture of the membranes, preterm birth, and small for gestational age, and low-birth-weight infants.Data were available for 707 of 753 women (patients were excluded due to loss to follow-up or withdrawal of consent), of whom 355 received the antioxidant vitamins and 352 placebo. The 2 groups were similar in demographic characteristics. Of those with chronic hypertension, 52.8% were receiving antihypertensive therapy when they became pregnant. Compliance rates were 84.5% and 86.9% for the vitamin and placebo groups, respectively. In the vitamin group, 13.9% of patients developed preeclampsia compared with 15.6% in the placebo group. Within both groups, no significant differences in the frequency of preeclampsia between treatment or placebo groups were noted. Only the mean arterial pressure at enrollment was significantly associated with the development of preeclampsia. In patients without chronic hypertension, 6% of the study group and 2.4% in the placebo group developed severe preeclampsia, not a significant difference. No patient died. Two patients in each group developed HELLP syndrome.Rates of gestational diabetes (3.4% vs. 3.7%), abruptio placentae (1.1% vs. 2.3%), induction of labor (14.6% vs. 18.3%), and cesarean delivery (66.0% vs. 67.6%) were not significantly different between the study and placebo groups, respectively, Premature rupture of the membranes occurred more frequently in the study patients than in the placebo group (10.6% vs. 5.5%, P = 0.015) The groups did not differ significantly in the rate of fetal and neonatal deaths, preterm delivery, low birth weight, small for gestational age, low Apgar scores at 1 and 5 minutes, and neonatal morbidities. Seven patients in the study group and 6 in the placebo group stopped taking the pills because of perceived side effects, including itching, eczema, vomiting, abdominal pain with or without diarrhea, headache, constipation, malaise, and diminished vision. One fetus in t...

BackgroundIntensive care unit (ICU) admission triage is performed routinely and is often based solely on clinical judgment, which could mask biases. A computerized algorithm to aid ICU triage decisions was developed to classify patients into the Society of Critical Care Medicine’s prioritization system. In this study, we sought to evaluate the reliability and validity of this algorithm.MethodsNine senior physicians evaluated forty clinical vignettes based on real patients. The reference standard was defined as the priorities ascribed by two investigators with full access to patients’ records. Agreement of algorithm-based priorities with the reference standard and with intuitive priorities provided by the physicians were evaluated. Correlations between algorithm prioritization and physicians’ judgment of the appropriateness of ICU admissions in scarcity and nonscarcity settings were also evaluated. Validity was further assessed by retrospectively applying this algorithm to 603 patients with requests for ICU admission for association with clinical outcomes.ResultsAgreement between algorithm-based priorities and the reference standard was substantial, with a median κ of 0.72 (interquartile range [IQR] 0.52–0.77). Algorithm-based priorities demonstrated higher interrater reliability (overall κ 0.61, 95 % confidence interval [CI] 0.57–0.65; median percentage agreement 0.64, IQR 0.59–0.70) than physicians’ intuitive prioritization (overall κ 0.51, 95 % CI 0.47–0.55; median percentage agreement 0.49, IQR 0.44–0.56) (p = 0.001). Algorithm-based priorities were also associated with physicians’ judgment of appropriateness of ICU admission (priorities 1, 2, 3, and 4 vignettes would be admitted to the last ICU bed in 83.7 %, 61.2 %, 45.2 %, and 16.8 % of the scenarios, respectively; p < 0.001) and with actual ICU admission, palliative care consultation, and hospital mortality in the retrospective cohort.ConclusionsThis ICU admission triage algorithm demonstrated good reliability and validity. However, more studies are needed to evaluate a difference in benefit of ICU admission justifying the admission of one priority stratum over the others.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1262-0) contains supplementary material, which is available to authorized users.

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BackgroundIntradialytic hypotension, a complication of intermittent hemodialysis, decreases the efficacy of dialysis and increases long-term mortality. This study was aimed to determine whether different predialysis ultrasound cardiopulmonary profiles could predict intradialytic hypotension.MethodsThis prospective observational single-center study was performed in 248 critically ill patients with acute kidney injury undergoing intermittent hemodialysis. Immediately before hemodialysis, vena cava collapsibility was measured by vena cava ultrasound and pulmonary congestion by lung ultrasound. Factors predicting intradialytic hypotension were identified by multiple logistic regression analysis.ResultsIntradialytic hypotension was observed in 31.9% (n = 79) of the patients, interruption of dialysis because of intradialytic hypotension occurred in 6.8% (n = 31) of the sessions, and overall 28-day mortality was 20.1% (n = 50). Patients were classified in four ultrasound profiles: (A) 108 with B lines > 14 and vena cava collapsibility > 11.5 mm m−2, (B) 38 with B lines < 14 and vena cava collapsibility ≤ 11.5 mm m−2, (C) 36 with B lines > 14 and vena cava collapsibility Di ≤ 11.5 mm m−2, and (D) 66 with B lines < 14 and vena cava collapsibility > 11.5 mm m−2. There was an increased risk of intradialytic hypotension in patients receiving norepinephrine (odds ratios = 15, p = 0.001) and with profiles B (odds ratios = 12, p = 0.001) and C (odds ratios = 17, p = 0.001).ConclusionIn critically ill patients on intermittent hemodialysis, the absence of hypervolemia as assessed by lung and vena cava ultrasound predisposes to intradialytic hypotension and suggests alternative techniques of hemodialysis to provide better hemodynamic stability.