Bloodstream Infections in Infants and Children With Congenital Heart Disease Undergoing Cardiac Surgery.

BACKGROUND: Children with congenital heart disease undergoing cardiac surgery are at risk for laboratory-confirmed bloodstream infections (LCBIs). These infections can lead to morbidity, mortality, and increased health care costs. The role of mucosal barrier injury in causing LCBIs is unknown. OBJECTIVES: To describe characteristics of LCBIs in patients admitted to cardiac intensive care and step-down units and to assess frequencies of National Healthcare Safety Network infection types and associations with organism classification, patient clinical factors, and infection outcomes. METHODS: A retrospective cohort analysis using manual electronic medical record data abstraction included children with congenital heart disease who developed an LCBI while receiving inpatient cardiac care between August 2011 and November 2018 at one institution. Demographic, clinical, laboratory, and outcome variables were collected and analyzed with descriptive and inferential statistics. RESULTS: Eighty-seven patients with congenital heart disease developed 103 LCBIs during the study time frame. The most common causative microorganisms were gram-positive bacteria, including Enterococcus faecalis and Staphylococcus epidermidis. Sixty-three percent of causative organisms were characterized as originating from mucosal barrier injury, although no infections met National Healthcare Safety Network criteria for mucosal barrier injury LCBIs. CONCLUSIONS: Translocation of bacteria through injured gut mucosa may cause bloodstream infections in children with congenital heart disease. Further investigation is warranted to understand microbiome changes that adversely select pathogenic gut organisms. Preventive care to maintain intact gut function and a healthy microbiome should be explored for this patient population.

Nocturnal polysomnographic correlates of daytime sleepiness.

The relations of nighttime polysomnographic sleep variables with daytime sleepiness scores on the Epworth Sleepiness Scale were assessed in a retrospective chart review of 38 patients referred to a sleep clinic. Of the variables assessed, only slow wave sleep was statistically significantly correlated with daytime sleepiness, regardless of whether the analysis was based on absolute minutes of slow wave sleep or percentage of total sleep time spent in slow wave sleep. Stepwise linear regression suggested that other polysomnographic variables did not provide additional predictive value beyond the two indices of slow wave sleep. Apparently, reduced quantity of slow wave sleep was weakly but significantly related to increased daytime sleepiness among these sleep-clinic patients.

Sleep disruptions among returning combat veterans from Iraq and Afghanistan.

BACKGROUND: Post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) are common injuries among returning combat veterans from the wars in Iraq and Afghanistan. Although these combat injuries have been associated with increased sleep disruption, little is known about the nature and specificity of sleep problems within these common injury categories. METHOD: A retrospective chart review of 69 consecutive referrals to the Waiter Reed Army Medical Center sleep clinic was conducted. All cases were active duty soldiers who had recently returned from combat deployment in Iraq or Afghanistan. Data from polysomnographically (PSG) recorded sleep stages, sleepiness scales, and documented medical diagnoses were extracted from medical records. Sleep data were compared across diagnoses of PTSD, TBI, and other clinical conditions. RESULTS: As expected, clinical sleep disturbances, including rates of obstructive sleep apnea, excessive awakenings, daytime sleepiness, and hypoxia, were high for the sample as a whole. However, no differences across diagnostic groups were found. Differences were observed, however, on PSG measures of sleep quality, suggesting more frequent arousals from sleep among patients with PTSD and greater slow wave sleep among those with TBI. Except for REM latency, medication status had virtually no effect on sleep variables. CONCLUSIONS: Among recently redeployed combat veterans, clinically significant sleep disturbances and problems with sleep-disordered breathing are common but nonspecific findings across primary diagnoses of PTSD, TBI, major depression, and anxiety disorder, whereas more subtle differences in sleep architecture and arousals as measured by overnight PSG recordings were modestly, but significantly, effective at distinguishing among the diagnostic groups.

Oral appliance titration in patients with obstructive sleep apnea induces the appearance of periodic limb movements.

STUDY OBJECTIVES: Oral appliance (OA) therapy is considered a first line choice of therapy for some patients with mild or moderate obstructive sleep apnea (OSA) and an alternative form of treatment in those intolerant of continuous positive airway pressure (CPAP) use. According to several studies, periodic limb movements (PLM) appear during effective treatment of OSA with CPAP, but a similar phenomenon has not been described with the use of oral appliance. Herein, we describe the incidence of PLM in patients with OSA who underwent oral appliance therapy titration. DESIGN: This is a retrospective, [corrected] observational study set in a six-bed sleep center in an academic, military referral hospital. PATIENTS AND METHODS: Patients with OSA (n=21; 15 men and six women; mean age, 43 years; and age range, 25 to 53 years) treated with OA during a 1-year period were analyzed. [corrected] Patients were categorized according to the severity of sleep apnea and incidence of PLM on diagnostic polysomnography. Effective treatment of OSA and appearance or disappearance of PLM with arousal on subsequent oral appliance titration polysomnography were recorded and compared. RESULTS: Twenty-one patients were included in the analysis. [corrected] During baseline polysomnography, three of 21 (14%) patients had five or more PLM with arousal per hour while 11 of 21 (52%) patients had PLM with arousal during the oral appliance titration trial. CONCLUSION: Oral appliance therapy for obstructive sleep apnea is an effective treatment and ideal for use in military recruits. The appearance of periodic limb movements with arousal during oral appliance use should be considered as a cause of persistent daytime sleepiness despite effective treatment of obstructive sleep apnea in this subset of patients.

Prone ventilation in a United States Marine with acute respiratory distress syndrome and an open abdominal injury.

A United States Marine with an open abdominal injury from a single gunshot wound to the chest and abdomen was placed in the prone position after suffering from acute respiratory distress syndrome (ARDS). Prone ventilation in traumatic injuries involving an open abdomen has been rarely reported or attempted because of the potentially fatal complication of bowel dehiscence. Improvement of gas exchange in patients with ARDS has been shown to occur with prone ventilation when conventional modes of ventilation have failed. The patient benefited from a sustained improvement in oxygenation hours after return to the supine position allowing for his rapid transport to a higher echelon of care and definitive management.

Validation of forehead venous pressure as a measure of respiratory effort for the diagnosis of sleep apnea.

OBJECTIVES: The aim of the study was to validate the measurement of Forehead Venous Pressure derived from a single site on the forehead as an alternative to esophageal manometry and respiratory effort bands in the differential diagnosis of sleep apnea. METHODS: Fourteen subjects underwent a laboratory polysomnography concurrently with ARES Unicorder at Walter Reed Army Medical Center. Two-hundred respiratory events were selected by a scorer boarded in sleep medicine and classified into six event categories used in the differential diagnosis of sleep disordered breathing. Four sets of events were prepared, each containing airflow and one of four measures of respiratory effort (i.e., esophageal manometer, chest and abdomen bands, and forehead venous pressure). A second board-certified scorer scored each set of events twice while blinded to the type of the effort signal. RESULTS: The inter-rater Kappa scores across all event types indicated all four effort signals provided moderate agreement (kappa = 0.43-0.47). When comparing the intra-rater Kappa scores, the chest belt was superior (kappa = 0.88) to the esophageal manometry, FVP and abdomen belt (kappa = 0.78-0.82). The Kappa scores for the intra-rater comparison with the esophageal serving as the gold standard, FVP abdomen and chest all showed near perfect agreement (kappa = 0.81-0.86). The esophageal manometer and FVP provided slightly better inter-rater agreement in the detection of both obstructive hypopneas and apneas as compared to the chest and abdomen belts. There was a 20-30% drop in inter-rater reliability in the detection of flow-limitation and ventilation-change events compared to obstructive events, and all effort signals showed poor inter-rater agreement for central and mixed events. CONCLUSIONS: The results of the study suggest that the FVP can serve as an alternative to respiratory bands in the differential diagnosis of sleep disordered breathing, and in the recognition of patients appropriate for bilevel continuous positive airway pressure devices.

Successful lung transplantation from a donor with a saddle pulmonary embolus.

Pulmonary embolus has received scant attention as a contraindication to lung donation. Reported is a case of a saddle pulmonary embolus successfully treated with thrombolytics in a donor whose lung was ultimately successfully transplanted. Discussed are the theoretical likelihood of thromboembolus in potential lung donors and the possible implications of pulmonary embolism on donor selection and lung physiology around the time of transplantation.

Airway function in women: bronchial hyperresponsiveness, cough, and vocal cord dysfunction.

Bronchial hyperreactivity and cough are common medical problems that occur more frequently in women. Differences in size, hormonal effects, density, and sensitivity to receptors and psychologic factors may all play a role, which results in increased expression of upper and lower airway disease. The reason that VCD occurs more commonly in women is not clear but many of the same explanations regarding bronchial hyperreactivity and cough may apply.

Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin-based influenza vaccine derived from influenza A (H1N1)pdm09 virus: a Phase 1 dose-escalation study in healthy adults.

BACKGROUND: Novel influenza viruses continue to pose a potential pandemic threat worldwide. In recent years, plants have been used to produce recombinant proteins, including subunit vaccines. A subunit influenza vaccine, HAC1, based on recombinant hemagglutinin from the 2009 pandemic A/California/04/2009 (H1N1) strain of influenza virus, has been manufactured using a plant virus-based transient expression technology in Nicotiana benthamiana plants and demonstrated to be immunogenic and safe in pre-clinical studies (Shoji et al., 2011). METHODS: A first-in-human, Phase 1, single-center, randomized, placebo-controlled, single-blind, dose escalation study was conducted to investigate safety, reactogenicity and immunogenicity of an HAC1 formulation at three escalating dose levels (15 µg, 45 µg and 90 µg) with and without Alhydrogel(®), in healthy adults 18-50 years of age (inclusive). Eighty participants were randomized into six study vaccine groups, a saline placebo group and an approved monovalent H1N1 vaccine group. Recipients received two doses of vaccine or placebo (except for the monovalent H1N1 vaccine cohort, which received a single dose of vaccine, later followed by a dose of placebo). RESULTS: The experimental vaccine was safe and well tolerated, and comparable to placebo and the approved monovalent H1N1 vaccine. Pain and tenderness at the injection site were the only local solicited reactions reported following vaccinations. Nearly all adverse events were mild to moderate in severity. The HAC1 vaccine was also immunogenic, with the highest seroconversion rates, based on serum hemagglutination-inhibition and virus microneutralization antibody titers, in the 90 µg non-adjuvanted HAC1 vaccine group after the second vaccine dose (78% and 100%, respectively). CONCLUSIONS: This is the first study demonstrating the safety and immunogenicity of a plant-produced subunit H1N1 influenza vaccine in healthy adults. The results support further clinical investigation of the HAC1 vaccine as well as demonstrate the feasibility of the plant-based technology for vaccine antigen production.

DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity.

BACKGROUND: Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection. METHODOLOGY/PRINCIPAL FINDINGS: The vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea), possibly related to immunization, was severe (Grade 3), preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27%) were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44-817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5-102) and were not associated with protection. Ex vivo IFN-γ ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13-408; AMA1 348, range 88-1270) and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019). Flow cytometry identified predominant IFN-γ mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant. SIGNIFICANCE: The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%). Protection was associated with cell-mediated immunity to AMA1, with CSP probably contributing. Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection. TRIAL REGISTRATION: ClinicalTrials.govNCT00870987.