46 research outputs found

    Successful Internalization of a Chronic Biliary Cutaneous Fistula After Liver Transplantation: Deepithelializing the Fistula Tract

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    Biliary cutaneous fistulas are uncommon sequelae after biliary surgery and can be a source of significant morbidity. We describe a liver recipient who developed a biliary cutaneous fistula secondary to hepatic artery thrombosis; this subsequently drained for over 7 years. Through a novel approach, using the transabdominal fistula tract as a conduit, the fistula skin opening was deepithelialized and anastomosed to a jejunal loop, internally draining the tract. For over 7 years postoperatively, this internal drainage procedure has continued to function effectively. This approach may have value in internalizing longstanding biliary cutaneous fistulas in well-selected patients in whom there is no existing biliary ductal system or the existing system anatomically does not lend itself to restoration of functional internal drainage through conventional approaches

    Hospital-acquired Clostridium difficile-associated disease in the intensive care unit setting: epidemiology, clinical course and outcome

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    <p>Abstract</p> <p>Background</p> <p><it>Clostridium difficile</it>-associated disease (CDAD) is a serious nosocomial infection, however few studies have assessed CDAD outcome in the intensive care unit (ICU). We evaluated the epidemiology, clinical course and outcome of hospital-acquired CDAD in the critical care setting.</p> <p>Methods</p> <p>We performed a historical cohort study on 58 adults with a positive <it>C. difficile </it>cytotoxin assay result occurring in intensive care units.</p> <p>Results</p> <p>Sixty-two percent of patients had concurrent infections, 50% of which were bloodstream infections. The most frequently prescribed antimicrobials prior to CDAD were anti-anaerobic agents (60.3%). Septic shock occurred in 32.8% of CDAD patients. The in-hospital mortality was 27.6%. Univariate analysis revealed that SOFA score, at least one organ failure and age were predictors of mortality. Charlson score ≥3, gender, concurrent infection, and number of days with diarrhea before a positive <it>C. difficile </it>toxin assay were not significant predictors of mortality on univariate analysis. Independent predictors for death were SOFA score at infection onset (per 1-point increment, OR 1.40; CI95 1.13–1.75) and age (per 1-year increment, OR 1.10; CI95 1.02–1.19).</p> <p>Conclusion</p> <p>In ICU patients with CDAD, advanced age and increased severity of illness at the onset of infection, as measured by the SOFA score, are independent predictors of death.</p

    Outbreak of Pneumonia in the Setting of Fatal Pneumococcal Meningitis among US Army Trainees: Potential Role of Chlamydia pneumoniae Infection

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    <p>Abstract</p> <p>Background</p> <p>Compared to the civilian population, military trainees are often at increased risk for respiratory infections. We investigated an outbreak of radiologically-confirmed pneumonia that was recognized after 2 fatal cases of serotype 7F pneumococcal meningitis were reported in a 303-person military trainee company (Alpha Company).</p> <p>Methods</p> <p>We reviewed surveillance data on pneumonia and febrile respiratory illness at the training facility; conducted chart reviews for cases of radiologically-confirmed pneumonia; and administered surveys and collected nasopharyngeal swabs from trainees in the outbreak battalion (Alpha and Hotel Companies), associated training staff, and trainees newly joining the battalion.</p> <p>Results</p> <p>Among Alpha and Hotel Company trainees, the average weekly attack rates of radiologically-confirmed pneumonia were 1.4% and 1.2% (most other companies at FLW: 0-0.4%). The pneumococcal carriage rate among all Alpha Company trainees was 15% with a predominance of serotypes 7F and 3. <it>Chlamydia pneumoniae </it>was identified from 31% of specimens collected from Alpha Company trainees with respiratory symptoms.</p> <p>Conclusion</p> <p>Although the etiology of the outbreak remains unclear, the identification of both <it>S. pneumoniae </it>and <it>C. pneumoniae </it>among trainees suggests that both pathogens may have contributed either independently or as cofactors to the observed increased incidence of pneumonia in the outbreak battalion and should be considered as possible etiologies in outbreaks of pneumonia in the military population.</p

    Cluster-randomised trial to evaluate the 'Change for Life' mass media/ social marketing campaign in the UK

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    Social marketing campaigns offer a promising approach to the prevention of childhood obesity. Change4Life (C4L) is a national obesity prevention campaign in England. It included mass media coverage aiming to reframe obesity into a health issue relevant to all and provided the opportunity for parents to complete a brief questionnaire ('How are the Kids') and receive personalised feedback about their children's eating and activity. Print and online C4L resources were available with guidance about healthy eating and physical activity. The study aims were to examine the impact of personalised feedback and print material from the C4L campaign on parents' attitudes and behaviours about their children's eating and activity in a community-based cluster-randomised controlled trial

    Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection

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    Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns), well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001) and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB), induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with cardiac dysfunction in clinical and experimental sepsis and ultimately resulted in depressed cardiomyocyte contractile performance along with rhythm disturbance. Our study proposes a detailed molecular mechanism of pneumococcal toxin-induced cardiac injury and highlights the major translational potential of targeting circulating PLY to protect against cardiac complications during pneumococcal infections

    Human Nasal Challenge with Streptococcus pneumoniae Is Immunising in the Absence of Carriage

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    Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that are protective against carriage and disease. We challenged healthy adults intra-nasally with live 23F or 6B Streptococcus pneumoniae in two sequential cohorts and collected nasal wash, bronchoalveolar lavage (BAL) and blood before and 6 weeks after challenge. We hypothesised that both cohorts would successfully become colonised but this did not occur except for one volunteer. The effect of bacterial challenge without colonisation in healthy adults has not been previously assessed. We measured the antigen-specific humoral and cellular immune responses in challenged but not colonised volunteers by ELISA and Flow Cytometry. Antigen-specific responses were seen in each compartment both before and after bacterial challenge for both cohorts. Antigen-specific IgG and IgA levels were significantly elevated in nasal wash 6 weeks after challenge compared to baseline. Immunoglobulin responses to pneumococci were directed towards various protein targets but not capsular polysaccharide. 23F but not 6B challenge elevated IgG anti-PspA in BAL. Serum immunoglobulins did not increase in response to challenge. In neither challenge cohort was there any alteration in the frequencies of TNF, IL-17 or IFNγ producing CD4 T cells before or after challenge in BAL or blood. We show that simple, low dose mucosal exposure with pneumococci may immunise mucosal surfaces by augmenting anti-protein immunoglobulin responses; but not capsular or cellular responses. We hypothesise that mucosal exposure alone may not replicate the systemic immunising effect of experimental or natural carriage in humans

    Maternal restrictive feeding and eating in the absence of hunger among toddlers: a cohort study

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    Abstract Background Restrictive feeding by parents has been associated with greater eating in the absence of hunger (EAH) among children, a risk factor for obesity. However, few studies have examined the association between restrictive feeding and EAH longitudinally, raising questions regarding the direction of associations between restrictive feeding and child EAH. Our objective was to examine the bidirectional prospective associations between restrictive feeding and EAH among toddlers. Methods Low-income mother-child dyads (n = 229) participated when children were 21, 27, and 33 months old. Restriction with regard to food amount and food quality were measured with the Infant Feeding Styles Questionnaire. EAH was measured as kilocalories of food children consumed after a satiating meal. A cross-lagged analysis adjusting for child sex and weight-for-length z-score was used to simultaneously test cross-sectional and bidirectional prospective associations between each type of restriction and children’s EAH. Results At 21 months, mothers of children with greater EAH reported higher restriction with regard to food amount (b = 0.17, p < .05). Restriction with regard to food amount at age 21 months was inversely associated with EAH at 27 months (b = −0.20, p < .05). Restriction with regard to food amount at 27 months was not associated with EAH at 33 months and restriction with regard to food quality was not associated with EAH. EAH did not prospectively predict maternal restriction. Conclusions Neither restriction with regard to food amount nor food quality increased risk for EAH among toddlers. Current US clinical practice recommendations for parents to avoid restrictive feeding, and the potential utility of restrictive feeding with regard to food amount in early toddlerhood, deserve further consideration.https://deepblue.lib.umich.edu/bitstream/2027.42/140394/1/12966_2017_Article_630.pd

    Impact of altering proximity on snack food intake in individuals with high and low executive function: study protocol.

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    BACKGROUND: Despite attempts to improve diet at population level, people living in material and social deprivation continue to consume unhealthy diets. Executive function - the ability to regulate behaviour and resist impulses - is weaker in individuals living in deprivation. Dietary interventions that educate and persuade people to reflect on and actively change behaviour may therefore disproportionately benefit individuals who are socioeconomically advantaged and have stronger executive function, thus exacerbating inequalities in health resulting from unhealthy diets. In contrast, manipulating environmental cues, such as how far away a food is placed, does not appeal to reasoned action and is thought to operate largely outside of awareness to influence behaviour. People eat more of a food when it is placed closer to them, an effect seemingly robust to context, food quality and body-weight status. However, previous studies of this 'proximity effect' are limited by small samples consisting mainly of university staff or students, biased towards higher socio-economic position and therefore likely stronger executive function. This study aims to test the hypothesis that placing food further away from a person decreases intake of that food regardless of executive function. METHODS/DESIGN: 156 members of the general public, recruited from low and high socio-economic groups, will be randomised to one of two conditions varying in the proximity of a snack food relative to their position: 20 cm or 70 cm. Participants are told they will be taking part in a relaxation study - and are fully debriefed at the conclusion of the session. The primary outcome is the proportion of participants eating any amount of snack food and the secondary outcome is the mean amount eaten. Executive function is assessed using the Stroop task. DISCUSSION: The proposed study takes a novel step by investigating the effect of proximity on snack food intake in a general population sample consisting of those with high and low executive function, appropriately powered to detect the predicted proximity effect. If this effect occurs irrespective of executive function and socio-economic position, it may have potential to reduce inequalities patterned by socio-economic position if implemented in real-world settings such as shops or restaurants. TRIAL REGISTRATION: Registered with the ISRCTN registry: ISRCTN46995850 on 07 October 2015.This study is supported by the Medical Research Council (MRC) and Sackler Prize, a doctoral training grant awarded to JAH. The study was also partially funded by the Department of Health Policy Research Program (Policy Research Unit in Behavior and Health [PR-UN-0409-10109]).This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s12889-016-3184-

    Vaccines based on the cell surface carbohydrates of pathogenic bacteria

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