Search

An effective vaccine against Pseudomonas aeruginosa would benefit people susceptible to severe infection. Vaccination targeting V antigen (PcrV) of the P. aeruginosa type III secretion system is a potential prophylactic strategy for reducing P. aeruginosa-induced acute lung injury and acute mortality. We created a recombinant protein (designated POmT) comprising three antigens: full-length PcrV (PcrV#1-#294), the outer membrane domain (#190-342) of OprF (OprF#190-#342), and a non-catalytic mutant of the carboxyl domain (#406-613) of exotoxin A (mToxA#406-#613(E553Δ)). In the combination of PcrV and OprF, mToxA, the efficacy of POmT was compared with that of single-antigen vaccines, two-antigen mixed vaccines, and a three-antigen mixed vaccine in a murine model of P. aeruginosa pneumonia. As a result, the 24 h-survival rates were 79%, 78%, 21%, 7%, and 36% in the POmT, PcrV, OprF, mTox, and alum-alone groups, respectively. Significant improvement in acute lung injury and reduction in acute mortality within 24 h after infection was observed in the POmT and PcrV groups than in the other groups. Overall, the POmT vaccine exhibited efficacy comparable to that of the PcrV vaccine. The future goal is to prove the efficacy of the POmT vaccine against various P. aeruginosa strains.

Antimicrobial-resistant Pseudomonas aeruginosa is an opportunistic pathogen that severely affects human health. Immunotherapy has attracted substantial attention as an alternative treatment to decrease antimicrobial drug use. Considering previous studies on antibody and vaccine therapy, we focused on quantifying antibodies specific to the V antigen (PcrV) and type III secretory protein (ExoU) expressed by P. aeruginosa to evaluate the serological immune response. We intratracheally infected male ICR mice with several P. aeruginosa strains and quantified antigen-specific antibody titers across 8 weeks. Intratracheal infection of P. aeruginosa PA103 at a sublethal dose decreased the body temperature of mice. The IgG and IgA serum titers against PcrV and ExoU did not increase over 8 weeks, and the IgM titer initially increased for 4 weeks and then decreased. Specific antibodies against PcrV and ExoU may be difficult to produce naturally. Therefore, the IgM expression against major secretory proteins of P. aeruginosa is critical.

Purpose: Mode decomposition is a method of extracting the characteristic intrinsic mode function (IMF) from various multidimensional time-series signals. Variational mode decomposition (VMD) searches for IMFs by optimizing the bandwidth to a narrow band with the norm while preserving the online estimated central frequency. In this study, we applied VMD to the electroencephalogram (EEG) analysis during general anesthesia. Methods: Using a bispectral index monitor, EEGs were recorded for 10 adult surgical patients (mean age ± sd: 43.7 ± 18.5 years) who were anesthetized with sevoflurane. We created an application named EEG Mode Decompositor, which decomposes the recorded EEG into IMFs and displays the Hilbert spectrogram. Results: During the 30-minute recovery from general anesthesia, the mean of the bispectral index increased from 45.4 ± 6.8 to 96.7 ± 1.5, whereas the central frequencies of IMF-1, IMF-2, IMF-3, IMF-4, IMF-5, and IMF-6 increased significantly from 0.35 ± 0.21 Hz to 0.18 ± 0.11 Hz, 1.54 ± 0.73 Hz to 5.32 ± 3.94 Hz, 5.79 ± 2.31 Hz to 15.64 ± 8.02 Hz, 10.34 ± 2.75 Hz to 26.13 ± 7.89 Hz, 14.23 ± 3.63 Hz to 35.50 ± 4.78 Hz, and 13.74 ± 5.42 Hz to 43.20 ± 3.16 Hz, respectively. Conclusion: The characteristic frequency component changes in the specific IMFs during emergence from general anesthesia were visually captured. EEG analysis by VMD is useful for extracting distinct changes in an EEG during general anesthesia.

Cyclic dinucleotides (CDNs) are secondary messengers composed of two purine nucleotides linked via two phosphodiester linkages: c-di-GMP, c-di-AMP, 3',3'-cGAMP, and 2',3'-cGAMP. CDNs activate the stimulator of interferon genes (STING) and trigger immune responses in mammalian species. CDNs are thus fascinating molecules as drug candidates, and chemically stable CDN analogues that act as STING agonists are highly desired at present. We herein report the practical synthesis of 4'-thiomodified c-di-AMP analogues, which have sulfur atoms at the 4'-position on the furanose ring instead of oxygen atoms, using simple phosphoramidite chemistry. The resulting 4'-thiomodified c-di-AMP analogues acted as potent STING agonists with long-term activity. Our results show that replacing O4' on CDNs with sulfur can lead to enhanced immunostimulatory effects via STING activation.

In recent years, numerous outbreaks of multidrug-resistant Pseudomonas aeruginosa have been reported across the world. Once an outbreak occurs, besides routinely testing isolates for susceptibility to antimicrobials, it is required to check their virulence genotypes and clonality profiles. Replacing pulsed-field gel electrophoresis DNA fingerprinting are faster, easier-to-use, and less expensive polymerase chain reaction (PCR)-based methods for characterizing hospital isolates. P. aeruginosa possesses a mosaic genome structure and a highly conserved core genome displaying low sequence diversity and a highly variable accessory genome that communicates with other Pseudomonas species via horizontal gene transfer. Multiple-locus variable-number tandem-repeat analysis and multilocus sequence typing methods allow for phylogenetic analysis of isolates by PCR amplification of target genes with the support of Internet-based services. The target genes located in the core genome regions usually contain low-frequency mutations, allowing the resulting phylogenetic trees to infer evolutionary processes. The multiplex PCR-based open reading frame typing (POT) method, integron PCR, and exoenzyme genotyping can determine a genotype by PCR amplifying a specific insertion gene in the accessory genome region using a single or a multiple primer set. Thus, analyzing P. aeruginosa isolates for their clonality, virulence factors, and resistance characteristics is achievable by combining the clonality evaluation of the core genome based on multiple-locus targeting methods with other methods that can identify specific virulence and antimicrobial genes. Software packages such as eBURST, R, and Dendroscope, which are powerful tools for phylogenetic analyses, enable researchers and clinicians to visualize clonality associations in clinical isolates.

Background: Accurate determination of the optimal insertion depth of a pediatric endotracheal tube (ETT) is quite important. The aim of this study was to create an easily available formula that can be used to determine the optimal insertion depth for a cuffed ETT even without depth marking with clear definitions of the upper and lower limits for the tip of ETT in the trachea in clinical practice. Methods: Eighty children under 12 years of age were enrolled. The depth marking of the cuffed ETT was placed at the vocal cords and both lungs were then auscultated using a stethoscope. The upper limit was radiographically defined as the position of the tip of the cuffed ETT being between the clavicles. The lower limit was defined as a distance of 5 mm above the carina. The relationship between the insertion depth and patient characteristics was analyzed to create a formula for optimal ETT insertion depth. Results: Sixty-nine ETTs were optimally placed in the trachea. There were good correlations between the optimal insertion depth of ETTs and patients characteristics (height (R = 0.92); BSA (R = 0.92); weight (R = 0.91); age (R = 0.88)). Using these patient characteristics, we created the following three formulas for calculation of the optimal insertion depth for pediatric cuffed ETTs: insertion depth (cm) = height (cm)/11 + 5.5, weight (kg)/3 + 9.5 or 11 + 3/4 × age (years). The rates of appropriate tube placement of both pediatric cuffed ETTs were 87.5% (Hi-Contour) and 85.0% (Microcuff). Conclusions: Our formula and graphs may be easy to determine the optimal insertion depth of cuffed ETT even without depth marking in clinical practice.

An effective vaccine against Pseudomonas aeruginosa would be hugely beneficial to people who are susceptible to the serious infections it can cause. Vaccination against PcrV of the P. aeruginosa type III secretion system is a potential prophylactic strategy for improving the incidence and prognosis of P. aeruginosa pneumonia. Here, the effect of nasal PcrV adjuvanted with CpG oligodeoxynucleotide (CpG) was compared with a nasal PcrV/aluminum hydroxide gel (alum) vaccine. Seven groups of mice were vaccinated intranasally with one of the following: 1, PcrV-CpG; 2, PcrV-alum; 3, PcrV alone; 4, CpG alone; 5, alum alone; 6 and 7, saline control. Fifty days after the first immunization, anti-PcrV IgG, IgA and IgG isotype titers were measured; significant increases in these titers were detected only in the PcrV-CpG vaccinated mice. The vaccinated mice were then intratracheally infected with a lethal dose of P. aeruginosa and their body temperatures and survival monitored for 24 hr, edema, bacteria, myeloperoxidase activity and lung histology also being evaluated at 24 hr post-infection. It was found that 73% of the PcrV-CpG-vaccinated mice survived, whereas fewer than 30% of the mice vaccinated with PcrV-alum or adjuvant alone survived. Lung edema and other inflammation-related variables were less severe in the PcrV-CpG group. The significant increase in PcrV-specific IgA titers detected following PcrV-CpG vaccination is probably a component of the disease protection mechanism. Overall, our data show that intranasal PcrV-CpG vaccination has potential efficacy for clinical application against P. aeruginosa pneumonia.

Cyclic dinucleotides (CDNs) are secondary messengers composed of two purine nucleotides linked via two phosphodiester linkages: c-di-GMP, c-di-AMP, 3′,3′-cGAMP, and 2′,3′-cGAMP. CDNs activate the stimulator of interferon genes (STING) and trigger immune responses in mammalian species. CDNs are thus fascinating molecules as drug candidates, and chemically stable CDN analogues that act as STING agonists are highly desired at present. We herein report the practical synthesis of 4′-thiomodified c-di-AMP analogues, which have sulfur atoms at the 4′-position on the furanose ring instead of oxygen atoms, using simple phosphoramidite chemistry. The resulting 4′-thiomodified c-di-AMP analogues acted as potent STING agonists with long-term activity. Our results show that replacing O4′ on CDNs with sulfur can lead to enhanced immunostimulatory effects via STING activation.

The Poincaré plot obtained from electroencephalography (EEG) has been used to evaluate the depth of anesthesia. A standalone EEG Analyzer application was developed; raw EEG signals obtained from a bispectral index (BIS) monitor were analyzed using an on-line monitoring system. Correlations between Poincaré plot parameters and other measurements associated with anesthesia depth were evaluated during emergence from inhalational general anesthesia. Of the participants, 20 were adults anesthetized with sevoflurane (adult_SEV), 20 were adults anesthetized with desflurane (adult_DES), and 20 were pediatric patients anesthetized with sevoflurane (ped_SEV). EEG signals were preprocessed through six bandpass digital filters (f0: 0.5–47 Hz, f1: 0.5–8 Hz, f2: 8–13 Hz, f3: 13–20 Hz, f4: 20–30 Hz, and f5: 30–47 Hz). The Poincaré plot-area ratio (PPAR = PPA_fx/PPA_f0, fx = f1∼f5) was analyzed at five frequency ranges. Regardless of the inhalational anesthetic used, there were strong linear correlations between the logarithm of PPAR at f5 and BIS (R2 = 0.67, 0.79, and 0.71, in the adult_SEV, adult_DES, and ped_SEV groups, respectively). As an additional observation, a part of EMG activity at the gamma range of 30–47 Hz probably influenced the calculations of BIS and PPAR_f5 with a non-negligible level. The logarithm of PPAR in the gamma band was most sensitive to state changes during the emergence process and could provide a new non-proprietary parameter that correlates with changes in BIS during measurement of anesthesia depth.

BackgroundAlthough the antiemetic effect of olanzapine on chemotherapy-induced nausea and vomiting has been characterized, the prophylactic role of olanzapine on postoperative nausea and vomiting (PONV) has not been fully elucidated. This clinical trial aims to examine the effectiveness of olanzapine for preventing PONV.MethodsPatients undergoing laparoscopic gynecological surgery at 5 university hospitals in Japan will be randomly assigned to receive either 5 mg of oral olanzapine or placebo 2 hours before the induction of anesthesia. All patients will receive intravenous dexamethasone at the induction of anesthesia. The primary outcome will be the incidence of postoperative nausea and vomiting within 24 hours after surgery. Secondary endpoints will include longitudinal changes in the incidence of postoperative nausea and vomiting and overall patient satisfaction.DiscussionThis trial will provide a high quality evidence whether olanzapine prevents PONV in gynecological laparoscopy patients at a high risk for PONV.Ethics and disseminationThe trial was approved by the institutional review board of the each participating study site. Study findings will be disseminated through peer-reviewed publications and in conference presentations.Trial registrationUMIN Clinical Trials Registry (UMIN-CTR) ID: 000022634, Registered on October 1, 2016 https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000026031

Antimicrobial-resistant isolates of Pseudomonas aeruginosa collected from 2005 to 2014 in a university hospital in Kyoto, Japan, were retrospectively analyzed by multilocus sequence typing (MLST), exoenzyme genotype determination, integron characterization, and clinical associations. During the study, 1573 P. aeruginosa isolates were detected, and 41 of these were resistant to more than two classes of antimicrobial agents. Twenty-five (61.0%) isolates were collected from urine. All isolates were resistant to ciprofloxacin, 8 (19.5%) isolates showed resistance to imipenem/cilastatin, and 8 (19.5%) isolates showed resistance to meropenem. None of the isolates fulfilled the clinical criteria for multidrug-resistant P. aeruginosa. All isolates were negative in the metallo-β lactamase test. Thirty-six (87.8%) isolates were of the exoS˗exoU+ genotype and 5 (12.2%) isolates were of the exoS+exoU˗ genotype. Among 36 exoS˗exoU+ isolates, 33 (80.5%) were ST357, and 3 (7.3%) were ST235. Five isolates of exoS+exoU˗ were ST186, ST244, ST314, ST508, and ST512. Thirty-three isolates were positive for class 1 integrons and four different class 1 integrons were detected: aminoglycoside (2′) adenyltransferase and chloramphenicol transporter (AadB+CmlA6), OXA-4 β-lactamase and aminoglycoside 3′-adenyltransferase (OXA4+AadA2), AadB alone, and aminoglycoside acetyltransferase alone (AacA31). Among the 41 patients from which the isolates originated, the most common underlying disease was cancer in 16 patients (39%), and 9 patients (22.0%) died during the hospitalization period. There was no statistical correlation between MLST, exoenzyme genotype, and patient mortality. The results indicated outbreaks of fluoroquinolone-resistant P. aeruginosa in immunocompromised patients mainly due to the propagation of potentially virulent ST357 isolates possessing the exoU+ genotype.

Vaccination against the type III secretion system of P. aeruginosa is a potential prophylactic strategy for reducing the incidence and improving the poor prognosis of P. aeruginosa pneumonia. In this study, the efficacies of three different adjuvants, Freund's adjuvant (FA), aluminum hydroxide (alum) and CpG oligodeoxynucleotide (ODN), were examined from the viewpoint of inducing PcrV-specific immunity against virulent P. aeruginosa. Mice that had been immunized intraperitoneally with recombinant PcrV formulated with one of the above adjuvants were challenged intratracheally with a lethal dose of P. aeruginosa. The PcrV-FA immunized group attained a survival rate of 91%, whereas the survival rates of the PcrV-alum and PcrV-CpG groups were 73% and 64%, respectively. In terms of hypothermia recovery after bacterial instillation, PcrV-alum was the most protective, followed by PcrV-FA and PcrV-CpG. The lung edema index was lower in the PcrV-CpG vaccination group than in the other groups. PcrV-alum immunization was associated with the greatest decrease in myeloperoxidase in infected lungs, and also decreased the number of lung bacteria to a similar number as in the PcrV-FA group. There was less neutrophil recruitment in the lungs of mice vaccinated with PcrV-alum or PcrV-CpG than in those of mice vaccinated with PcrV-FA or PcrV alone. Overall, in terms of mouse survival the PcrV-CpG vaccine, which could be a relatively safe next-generation vaccine, showed a comparable effect to the PcrV-alum vaccine.

The V-antigen, a virulence-associated protein, was first identified inYersinia pestismore than half a century ago. Since then, other V-antigen homologs and orthologs have been discovered and are now considered vital molecules for the toxic effects mediated by the type III secretion system in infections caused by various pathogenic Gram-negative bacteria. After purifying recombinant V-antigen proteins including PcrV fromPseudomonas aeruginosa, LcrV fromYersinia, LssV fromPhotorhabdus luminescens, AcrV fromAeromonas salmonicida, and VcrV fromVibrio parahaemolyticus, we developed an enzyme-linked immunoabsorbent assay to measure titers against each V-antigen in the sera collected from 186 adult volunteers. Different titer-specific correlation levels were determined for the five V-antigens. The anti-LcrV and anti-AcrV titers shared the highest correlation with each other, with a correlation coefficient of 0.84. The next highest correlation coefficient was between anti-AcrV and anti-VcrV titers at 0.79, while the lowest correlation was found between anti-LcrV and anti-VcrV titers, which were still higher than 0.7 Sera from mice immunized with one of the five recombinant V-antigens displayed cross-antigenicity with some of the other four V-antigens, supporting the results from the human sera. Thus, the serum anti-V-antigen titer measurement system could potentially be used for epidemiological investigations on various pathogenic Gram-negative bacteria.

The secondary in-hospital epidemiological investigation for drug-resistant Pseudomonas aeruginosa infections was conducted to evaluate the in-hospital situation and identify any associations between exoenzyme genotypes and other genotypes and antimicrobial resistance characteristics, at the University Hospital in Kyoto, Japan, following a reported outbreak of antimicrobial-resistant P. aeruginosa ST357 between 2005 and 2014. Twelve of the 546 P. aeruginosa isolates collected during the follow-up period were resistant to more than two classes of antimicrobials. All isolates were resistant to fluoroquinolones and 8 (66.7%) showed carbapenem resistance. None of the isolates fulfilled the clinical criteria for multidrug-resistant P. aeruginosa. All isolates were metallo-β-lactamase test-negative. Among five exoS (−)exoU (+) isolates, three possessing a class 1 integron with gene cassette aadB + cmlA6 were classified as ST357, and one isolate containing a class 1 integron with aacA31 was ST235. Collectively, the second survey results confirm that the initial outbreak is currently undergoing convergence. By combining data from the first and second surveys, we showed that prevalent STs such as ST357 and ST235 are associated with fluoroquinolone resistance, class 1 integron-associated resistance to β-lactams and aminoglycosides, and cytotoxic exoU (+) genotypes. With the current worldwide spread of ST357 and ST235 isolates, it is important to evaluate epidemiological trends for high-risk P. aeruginosa isolates by continuous hospital monitoring.

Arterial pulse waveform analysis (APWA) with a semi-invasive cardiac output monitoring device is popular in perioperative hemodynamic and fluid management. However, in APWA, evaluation of hemodynamic data is not well discussed. In this study, we analyzed how we visually interpret hemodynamic data, including stroke volume variation (SVV) and stroke volume (SV) derived from APWA. We performed arithmetic estimation of the SVV-SV relationship and applied measured values to this estimation. We then collected measured values in six anesthesia cases, including three liver transplantations and three other types of surgeries, to apply them to this SVV-SVI (stroke volume variation index) plot. Arithmetic analysis showed that the relationship between SVV and SV can be drawn as hyperbolic curves. Plotting SVV-SV values in the semi-logarithmic scale showed linear correlations, and the slopes of the linear regression lines theoretically represented average mean cardiac contractility. In clinical measurements in APWA, plotting SVV and SVI values in the linear scale and the semi-logarithmic scale showed the correlations represented by hyperbolic curves and linear regression lines. The plots approximately shifted on the rectangular hyperbolic curves, depending on blood loss and blood transfusion. Arithmetic estimation is close to real measurement of the SVV-SV interaction in hyperbolic curves. In APWA, using SVV as an index of preload and the cardiac index or SVI derived from arterial pressure-based cardiac output as an index of cardiac function, is likely to be appropriate for categorizing hemodynamic stages as a substitute for Forrester subsets.

Multi-drug resistant Pseudomonas aeruginosa causes the type of acute lung injury that is strongly associated with bacteremia, sepsis, and mortality, especially under immunocompromised conditions. Although administration of immunoglobulin solution is an applicable immunotherapy in immunocompromised patients, efficacy of immunoglobulin administration against multi-drug resistant P. aeruginosa pneumonia has not been well evaluated. In this study, we investigated the effectiveness of prophylactic administration of immunoglobulin solution (IVIG) in comparison with that of other types of antimicrobial agents, such as anti-PcrV IgG, piperacillin/tazobactam, or colistin in an immunocompromised mouse model of P. aeruginosa pneumonia. Colistin was the most effective agent for preventing acute lung injury, bacteremia, cytokinemia, and sepsis. Among the four tested antimicrobial agents, after colistin, anti-PcrV IgG and IVIG were the most effective at protecting mice from mortality. Piperacillin/tazobactam did not prevent acute lung injury or bacteremia; rather, it worsened lung histology. The data suggest that using an agent for which a positive result in an in vitro susceptibility test has been obtained may not always prevent acute lung injury in a leukopenic host infected with P. aeruginosa. Clinicians should consider the possibility of discrepancies between in vitro and in vivo tests because the absence of in vitro bactericidal activity in an antimicrobial agent is not always a reliable predictor of its lack of ability to eradicate bacteria in vivo, even in immunocompromised hosts. Based on our findings, the potential protective effects of IVIG against the acute lung injury induced by P. aeruginosa should be reevaluated.

Of the various virulence mechanisms of the opportunistic pathogen Pseudomonas aeruginosa, the type III secretion system (TTSS) has been characterized as a major factor associated with acute lung injury, bacteremia and mortality. In addition, PcrV, a component protein of the TTSS, has been characterized as a protective antigen against infection with P. aeruginosa. This study comprised an epidemiological analysis of serum anti-PcrV titers in a cohort of Japanese adults. From April 2012 to March 2013, serum anti-PcrV titers of 198 volunteer participants undergoing anesthesia for scheduled surgeries were measured. The median, minimum and maximum serum anti-PcrV titers among the 198 participants were 4.09 nM, 1.01 nM and 113.81 nM, respectively. The maximum peaks in the histogram were within the anti-PcrV 2.00-4.99 nM titer range; values for 115 participants (58.1%) were within this range. Anti-PcrV titers were more than approximately three-fold greater (>12 nM) than the median value in 21 participants (10.6%). Ten-year interval age increases, history of treatment for traffic trauma, and a history of past surgery each showed statistically significant associations with higher anti-PcrV titers (i.e., >10 nM) than did the other factors assessed by binomial analysis. This study revealed a considerable variation in anti-PcrV titers in adult subjects without any obvious histories of infection with P. aeruginosa.

Virulent and multidrug-resistant Pseudomonas aeruginosa causes a lethal pneumonia, especially in patients who are artificially ventilated. It has been reported that the virulence mechanism used by P. aeruginosa, which is linked to acute lung injury, is strongly associated with the type III secretion system, and specific antibodies targeting this system have shown a protective effect in both experimental and clinical settings. We investigated the effect of administering IV immunoglobulins on P. aeruginosa pneumonia, including its associated bacteremia and mortality, although focusing especially on type III secretion system-associated P. aeruginosa virulence.Prospective randomized and controlled animal study.University laboratory.Male ICR mice.Mice were infected intratracheally with a lethal dose of the virulent P. aeruginosa PA103 strain. IV immunoglobulin administration was examined in three different settings: 1) premixed; 2) pre-IV, prophylactic administration before bacterial infection; and 3) post-IV, therapeutic administration after bacterial infection. The effect of specific antigen titer depletion of IV immunoglobulins was also examined.Survival and body temperature were monitored for 24 hours. Bacteremia, cytokine concentration, myeloperoxidase activity, WBC counts in the blood, and lung bacterial load were evaluated. Survival improved significantly in mice that received IV immunoglobulins (p0.05). Lung edema, lung bacteriologic load, and bacteremia decreased significantly in the IV immunoglobulin-treated mice (p0.05). The mechanism of protection was associated with the presence of antibodies against both PcrV and some bacterial surface antigens in the IV immunoglobulins.IV immunoglobulin administration had a significantly protective effect against lethal infection from virulent P. aeruginosa. Prophylactic IV immunoglobulin administration at the highest dose was comparable with that achieved by administrating a specific anti-PcrV polyclonal IgG into the mice. The mechanism of protection is likely to involve the synergic action of anti-PcrV titers and antibodies against some surface antigen(s) that block the type III secretion system-associated virulence of P. aeruginosa.

We report a case of severe anaphylactic shock in a 5-month-old infant who was scheduled to undergo an external inguinal hernia repair under general anesthesia. Rocuronium used for anesthesia induction was the most likely cause of anaphylaxis. High levels of serum tryptase and histamine detected in the blood sample collected during the anaphylactic reaction confirmed the diagnosis of anaphylactic shock. The patient’s clinical status improved within 90 min of intervention by the intravenous injection of vasopressors and a steroid. Surgery was canceled, and the patient stayed in the pediatric intensive care unit (PICU) under artificial ventilation for 5 h before safe extubation. The patient achieved full recovery the next day, without any sequelae. The rescheduled surgery was successfully completed 5 months later under general anesthesia without the use of neuromuscular blocking agents.

An effective vaccine against Pseudomonas aeruginosa would be hugely beneficial to people who are susceptible to the serious infections it can cause. Vaccination against PcrV of the P. aeruginosa type III secretion system is a potential prophylactic strategy for improving the incidence and prognosis of P. aeruginosa pneumonia. Here, the effect of nasal PcrV adjuvanted with CpG oligodeoxynucleotide (CpG) was compared with a nasal PcrV/aluminum hydroxide gel (alum) vaccine. Seven groups of mice were vaccinated intranasally with one of the following: 1, PcrV-CpG; 2, PcrV-alum; 3, PcrV alone; 4, CpG alone; 5, alum alone; 6 and 7, saline control. Fifty days after the first immunization, anti-PcrV IgG, IgA and IgG isotype titers were measured; significant increases in these titers were detected only in the PcrV-CpG vaccinated mice. The vaccinated mice were then intratracheally infected with a lethal dose of P. aeruginosa and their body temperatures and survival monitored for 24 hr, edema, bacteria, myeloperoxidase activity and lung histology also being evaluated at 24 hr post-infection. It was found that 73% of the PcrV-CpG-vaccinated mice survived, whereas fewer than 30% of the mice vaccinated with PcrV-alum or adjuvant alone survived. Lung edema and other inflammation-related variables were less severe in the PcrV-CpG group. The significant increase in PcrV-specific IgA titers detected following PcrV-CpG vaccination is probably a component of the disease protection mechanism. Overall, our data show that intranasal PcrV-CpG vaccination has potential efficacy for clinical application against P. aeruginosa pneumonia.

Background Vector flow mapping, a novel flow visualization echocardiographic technology, is increasing in popularity. Energy loss reference values for children have been established using vector flow mapping, but those for adults have not yet been provided. We aimed to establish reference values in healthy adults for energy loss, kinetic energy in the left ventricular outflow tract, and the energetic performance index (defined as the ratio of kinetic energy to energy loss over one cardiac cycle). Methods Transthoracic echocardiography was performed in fifty healthy volunteers, and the stored images were analyzed to calculate energy loss, kinetic energy, and energetic performance index and obtain ranges of reference values for these. Results Mean energy loss over one cardiac cycle ranged from 10.1 to 59.1 mW/m (mean ± SD, 27.53 ± 13.46 mW/m), with a reference range of 10.32 ~ 58.63 mW/m. Mean systolic energy loss ranged from 8.5 to 80.1 (23.52 ± 14.53) mW/m, with a reference range of 8.86 ~ 77.30 mW/m. Mean diastolic energy loss ranged from 7.9 to 86 (30.41 ± 16.93) mW/m, with a reference range of 8.31 ~ 80.36 mW/m. Mean kinetic energy in the left ventricular outflow tract over one cardiac cycle ranged from 200 to 851.6 (449.74 ± 177.51) mW/m with a reference range of 203.16 ~ 833.15 mW/m. The energetic performance index ranged from 5.3 to 37.6 (18.48 ± 7.74), with a reference range of 5.80 ~ 36.67. Conclusions Energy loss, kinetic energy, and energetic performance index reference values were defined using vector flow mapping. These reference values enable the assessment of various cardiac conditions in any clinical situation.

Background Staged palliative surgery markedly shifts the balance of volume load on a single ventricle and pulmonary vascular bed. Blalock-Taussig shunt necessitates a single ventricle eject blood to both the systemic and pulmonary circulation. On the contrary, bidirectional cavopulmonary shunt release the single ventricle from pulmonary circulation. Case presentation We report a case of tricuspid atresia patient who underwent first palliative surgery and second palliative surgery. Volume loading condition was assessed by energetic parameters (energy loss, kinetic energy) intraoperatively using vector flow mapping. These energetic parameters can simply indicate the volume loading condition. Conclusion Vector flow mapping was useful tool for monitoring volume loading condition in congenital heart disease surgery. Electronic supplementary material The online version of this article (10.1186/s12947-017-0118-3) contains supplementary material, which is available to authorized users.

Vector flow mapping, a novel flow visualization echocardiographic technology, is increasing in popularity. Energy loss reference values for children have been established using vector flow mapping, but those for adults have not yet been provided. We aimed to establish reference values in healthy adults for energy loss, kinetic energy in the left ventricular outflow tract, and the energetic performance index (defined as the ratio of kinetic energy to energy loss over one cardiac cycle). Transthoracic echocardiography was performed in fifty healthy volunteers, and the stored images were analyzed to calculate energy loss, kinetic energy, and energetic performance index and obtain ranges of reference values for these. Mean energy loss over one cardiac cycle ranged from 10.1 to 59.1 mW/m (mean ± SD, 27.53 ± 13.46 mW/m), with a reference range of 10.32 ~ 58.63 mW/m. Mean systolic energy loss ranged from 8.5 to 80.1 (23.52 ± 14.53) mW/m, with a reference range of 8.86 ~ 77.30 mW/m. Mean diastolic energy loss ranged from 7.9 to 86 (30.41 ± 16.93) mW/m, with a reference range of 8.31 ~ 80.36 mW/m. Mean kinetic energy in the left ventricular outflow tract over one cardiac cycle ranged from 200 to 851.6 (449.74 ± 177.51) mW/m with a reference range of 203.16 ~ 833.15 mW/m. The energetic performance index ranged from 5.3 to 37.6 (18.48 ± 7.74), with a reference range of 5.80 ~ 36.67. Energy loss, kinetic energy, and energetic performance index reference values were defined using vector flow mapping. These reference values enable the assessment of various cardiac conditions in any clinical situation.

Vaccination against the type III secretion system of P. aeruginosa is a potential prophylactic strategy for reducing the incidence and improving the poor prognosis of P. aeruginosa pneumonia. In this study, the efficacies of three different adjuvants, Freund's adjuvant (FA), aluminum hydroxide (alum) and CpG oligodeoxynucleotide (ODN), were examined from the viewpoint of inducing PcrV-specific immunity against virulent P. aeruginosa. Mice that had been immunized intraperitoneally with recombinant PcrV formulated with one of the above adjuvants were challenged intratracheally with a lethal dose of P. aeruginosa. The PcrV-FA immunized group attained a survival rate of 91%, whereas the survival rates of the PcrV-alum and PcrV-CpG groups were 73% and 64%, respectively. In terms of hypothermia recovery after bacterial instillation, PcrV-alum was the most protective, followed by PcrV-FA and PcrV-CpG. The lung edema index was lower in the PcrV-CpG vaccination group than in the other groups. PcrV-alum immunization was associated with the greatest decrease in myeloperoxidase in infected lungs, and also decreased the number of lung bacteria to a similar number as in the PcrV-FA group. There was less neutrophil recruitment in the lungs of mice vaccinated with PcrV-alum or PcrV-CpG than in those of mice vaccinated with PcrV-FA or PcrV alone. Overall, in terms of mouse survival the PcrV-CpG vaccine, which could be a relatively safe next-generation vaccine, showed a comparable effect to the PcrV-alum vaccine.

BackgroundRocuronium induces venous pain and the withdrawal reflex during injection. MR13A10A, generic rocuronium with a novel solution, reduced the injection-induced withdrawal reflex in rodents. We hypothesized that MR13A10A would reduce the frequency and severity of injection-induced withdrawal reflexes compared with original rocuronium during clinical anesthesia induction.MethodsThis prospective, open (but assessor-blinded), randomized, controlled study was conducted at a single academic hospital. The assessor was blinded to the study condition in order to minimize observer bias. Participants were allocated to either MR13A10A or traditional formula groups by a blocked stratified randomization method. Participants in the MR13A10A group received MR13A10A, whereas the original rocuronium group received the same amount of original rocuronium. The primary outcome was presence of the withdrawal reflex after rocuronium injection. Severity of the withdrawal reflex, changes in blood pressure and heart rate, and the train of four (TOF) ratio were measured as secondary outcomes. The withdrawal reflex was assessed using a video recording in a blinded manner.ResultsOf the 149 participants, 76 were allocated to the MR13A10A group and 73 to the original rocuronium group. The frequency of the withdrawal reflex was significantly lower with MR13A10A compared with original rocuronium (19.7% and 54.8% for MR13A10A and original rocuronium groups, respectively, pConclusionThe frequency and severity of the withdrawal reflex after injection were significantly reduced by using MR13A10A. MR13A10A might contribute to safe and less invasive anesthesia management.

Objectives We assessed vortex patterns and energy loss in left ventricular flow in patients who underwent mitral valve repair or replacement with bioprosthetic valves. Methods Vector flow mapping was performed before and after the procedure in 15 and 17 patients who underwent repair and replacement, respectively. The preprocedure mitral-septal angle was measured in all patients. Relationships between vortex patterns or energy loss change (ELC) and annuloplasty ring or bioprosthetic valve sizes or the effect of mitral leaflet resection in the repair group were statistically analysed. Results Normal vortex patterns were observed in 13 and 1 patients who underwent repair and replacement, respectively. Abnormal vortex patterns were observed in 2 and 16 patients who underwent repair and replacement, respectively. ELC was significantly higher in the replacement group (196.6 ± 180.8) than in the repair group (71.9 ± 43.9). In the repair group, preoperative mitral-septal angles in patients with normal vortex patterns (79.2° ± 3.4°) were significantly larger than those in patients with abnormal vortex patterns (67.5° ± 3.5°). No significant differences were observed in the effects of annuloplasty ring and bioprosthetic valve sizes on vortex patterns and ELC, and in the effect of mitral valve resection (80.4 ± 56.3) and respect (without leaflet resection) (53.8 ± 28.4) on ELC in the repair group. Conclusions Mitral valve replacement alters the intraventricular vortex pattern and increases flow energy loss. A small mitral-septal angle is a risk factor for abnormal vortex patterns after mitral valve repair surgery.