Impact of Oral Chlorhexidine on Bloodstream Infection in Critically Ill Patients: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Oropharyngeal overgrowth of microorganisms in the critically ill is a risk factor for lower respiratory tract infection and subsequent invasion of the bloodstream. Oral chlorhexidine has been used to prevent pneumonia, but its effect on bloodstream infection never has been assessed in meta-analyses. The authors explored the effect of oral chlorhexidine on the incidence of bloodstream infection, the causative microorganism, and on all-cause mortality in critically ill patients. DESIGN: Systematic review and meta-analysis of published studies. SETTING: Intensive care unit. PARTICIPANTS: The study comprised critically ill patients receiving oral chlorhexidine (test group) and placebo or standard oral care (control group). INTERVENTIONS: PubMed and the Cochrane Register of Controlled Trials were searched. Odds ratios (ORs) were pooled using the random-effects model. MEASUREMENTS AND MAIN RESULTS: Five studies including 1,655 patients (832 chlorhexidine and 823 control patients) were identified. The majority of information was from studies at low or unclear risk bias; 1 study was at high risk of bias. Bloodstream infection and mortality were not reduced significantly by chlorhexidine (OR 0.74; 95% confidence interval [CI] 0.37-1.50 and OR 0.69; 95% CI 0.31-1.53, respectively). In the subgroup of surgical, mainly cardiac, patients, chlorhexidine reduced bloodstream infection (OR 0.47; 95% CI 0.22-0.97). Chlorhexidine did not affect any microorganism significantly. CONCLUSION: In critically ill patients, oropharyngeal chlorhexidine did not reduce bloodstream infection and mortality significantly and did not affect any microorganism involved. The presence of a high risk of bias in 1 study and unclear risk of bias in others may have affected the robustness of these findings.

One-pot synthesis of cinnamylideneacetophenones and their in vitro cytotoxicity in breast cancer cells.

A series of cinnamylideneacetophenones were synthesized via a modified Claisen-Schmidt condensation reaction and evaluated for cytotoxicity against breast cancer cells using the Alamar Blue™ assay. Derivatives 17 and 18 bearing a 2-nitro group on the B ring, exhibited sub-micromolar cytotoxicity in MCF-7 cells (IC50=71 and 1.9 nM), respectively. Derivative 17 also displayed sub-micromolar (IC50=780 nM) cytotoxicity in MDA-MB-468 cells. Additionally, 17 and 18 displayed significantly less cytotoxicity than the chemotherapeutic doxorubicin in non-tumorigenic MCF-10A cells. This study provides evidence supporting the continued development of nitro-substituted cinnamylideneacetophenones as small molecules to treat breast cancer.

Selective decontamination of the digestive tract in critically ill children: systematic review and meta-analysis.

OBJECTIVE: We examined the impact of selective decontamination of the digestive tract on morbidity and mortality in critically ill children. DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, and previous meta-analyses. STUDY SELECTION: We included all randomized controlled trials comparing administration of enteral antimicrobials in selective decontamination of the digestive tract with or without a parenteral component with placebo or standard therapy used in the controls. DATA EXTRACTION: The primary end point was the number of acquired pneumonias. Secondary end points were number of infections and overall mortality. Odds ratios were pooled with the random effect model. DATA SYNTHESIS: Four randomized controlled trials including 335 patients were identified. Pneumonia was diagnosed in five of 170 patients (2.9%) for selective decontamination of the digestive tract and 16 of 165 patients (9.7%) for controls (odds ratio 0.31; 95% confidence interval 0.11-0.87; p = .027). Overall mortality for selective decontamination of the digestive tract was 13 of 170 (7.6%) vs. control, 11 of 165 (6.7%) (odds ratio 1.18; 95% confidence interval 0.50-2.76; p = .70). In three studies (n = 109), infection occurred in ten of 54 (18.5%) patients on selective decontamination of the digestive tract and 24 of 55 (43.6%) in the controls (odds ratio 0.34; 95% confidence interval 0.05-2.18; p = .25). CONCLUSIONS: In the four available pediatric randomized controlled trials, selective decontamination of the digestive tract significantly reduced the number of children who developed pneumonia.

Identification of normal cranial sutures in infants on routine magnetic resonance imaging.

There are increasing concerns relating to the ionizing effects of computed tomography imaging in infants with benign conditions. Magnetic resonance imaging (MRI) is a potential alternative to ionizing radiation when determining patency of the cranial sutures; however, there is no documentation in the literature on the appearance of normal cranial sutures in infants on MRI. This study reviews the appearance of the cranial sutures, their widths, and accuracy of identification in the first year of life on MRI.The coronal, sagittal, and lambdoid sutures were evaluated by 5 assessors on 100 anonymized MRI scans in infants aged 1 to 361 days. The sutures were scored on a 3-point scale. The MRI sequences investigated were axial T1, axial T2, coronal fluid attenuated inversion recovery, axial short tau inversion recovery, and sagittal T1. The suture widths were measured in those cases where they were clearly identifiable, and agreement was obtained in the first aspect of the study (n = 38).A κ score of 0.6 was obtained for interrater agreement. An increasing total score for all sutures with advancing age was found (P < 0.05). The mean suture widths for the coronal, sagittal, and lambdoid sutures were 1.2 (SD, 0.4), 1.4 (SD, 0.4), and 1.3 (SD, 0.3) mm, respectively. There was no significant difference in suture width with age.The appearance of cranial sutures on MRI is as an area of signal void, which may be difficult to clearly define, thus making it unreliable as a standard investigation in the diagnosis of craniosynostosis.

A study evaluating quality of life and factors affecting it before, during and after menopause.

OBJECTIVE: To determine if quality of life (QoL) changes before, during and after menopause and whether these changes are linked to symptoms, demographics, and/or lifestyle factors. METHODS: We undertook a cross-sectional online survey. We invited women aged between 35 and 60 years to complete the survey which included the Short-Form 36 (SF-36) generic quality of life measure, the menopause specific Utian-Quality of life (UQOL) measure, and questions about health and wellbeing, menopause symptoms and hormonal stage. The data were analysed with one-way ANOVA analysis and multivariate regression modelling. RESULTS: 279 women completed the survey. Most were aged between 51 and 55 years. In the unadjusted analysis there was a tendency for QoL to deteriorate from pre to peri to menopause and then increase slightly post menopause. This was however not significant in multivariate analysis. Multivariate analysis identified that lifestyle factors significantly influenced QoL. Regular exercise resulted in better QoL scores across a number of the UQol and SF-36 sub-scales. Being very overweight and having more menopause symptoms resulted in worse QoL. CONCLUSIONS: Although there was a trend towards worse quality of life in the peri and menopause stages this was not significantly different in adjusted multivariate analyses. Those experiencing more symptoms had significantly worse QoL. Lifestyle factors may affect QoL, but the picture is not straightforward. It is promising that there was a trend toward improved QoL in the post-menopausal stage. These findings should inform education material and promote awareness of the menopause and its impact on QoL. (245).

Oxygen-enhanced MRI and radiotherapy in patients with oropharyngeal squamous cell carcinoma.

Background and purpose: This study aimed to assess the role of T1 mapping and oxygen-enhanced MRI in patients undergoing radical dose radiotherapy for HPV positive oropharyngeal cancer, which has not yet been examined in an OE-MRI study. Materials and methods: Variable Flip Angle T1 maps were acquired on a 3T MRI scanner while patients (n = 12) breathed air and/or 100 % oxygen, before and after fraction 10 of the planned 30 fractions of chemoradiotherapy ('visit 1' and 'visit 2', respectively). The analysis aimed to assess to what extent (1) native R1 relates to patient outcome; (2) OE-MRI response relates to patient outcome; (3) changes in mean R1 before and after radiotherapy related to clinical outcome in patients with oropharyngeal squamous cell carcinoma. Results: Due to the radiotherapy being largely successful, the sample sizes of non-responder groups were small, and therefore it was not possible to properly assess the predictive nature of OE-MRI. The tumour R1 increased in some patients while decreasing in others, in a pattern that was overall consistent with the underlying OE-MRI theory and previously reported tumour OE-MRI responses. In addition, we discuss some practical challenges faced when integrating this technique into a clinical trial, with the aim that sharing this is helpful to researchers planning to use OE-MRI in future clinical studies. Conclusion: Altogether, these results suggest that further clinical OE-MRI studies to assess hypoxia and radiotherapy response are worth pursuing, and that there is important work to be done to improve the robustness of the OE-MRI technique in human applications in order for it to be useful as a widespread clinical technique.

Using Variable Flip Angle (VFA) and Modified Look-Locker Inversion Recovery (MOLLI) T1 mapping in clinical OE-MRI.

BACKGROUND AND PURPOSE: The imaging technique known as Oxygen-Enhanced MRI is under development as a noninvasive technique for imaging hypoxia in tumours and pulmonary diseases. While promising results have been shown in preclinical experiments, clinical studies have mentioned experiencing difficulties with patient motion, image registration, and the limitations of single-slice images compared to 3D volumes. As clinical studies begin to assess feasibility of using OE-MRI in patients, it is important for researchers to communicate about the practical challenges experienced when using OE-MRI on patients to help the technique advance. MATERIALS AND METHODS: We report on our experience with using two types of T1 mapping (MOLLI and VFA) for a recently completed OE-MRI clinical study on oropharyngeal squamous cell carcinoma. RESULTS: We report: (1) the artefacts and practical difficulties encountered in this study; (2) the difference in estimated T1 from each method used - the VFA T1 estimation was higher than the MOLLI estimation by 27% on average; (3) the standard deviation within the tumour ROIs - there was no significant difference in the standard deviation seen within the tumour ROIs from the VFA versus MOLLI; and (4) the OE-MRI response collected from either method. Lastly, we collated the MRI acquisition details from over 45 relevant manuscripts as a convenient reference for researchers planning future studies. CONCLUSION: We have reported our practical experience from an OE-MRI clinical study, with the aim that sharing this is helpful to researchers planning future studies. In this study, VFA was a more useful technique for using OE-MRI in tumours than MOLLI T1 mapping.

Antibiotic-resistant bacteria and infection in children with cerebral palsy requiring mechanical ventilation.

INTRODUCTION: Severe and chronic illness can alter the bacterial flora carried in the oropharynx and gut. There are little data on the bacterial flora of children with chronic neurologic impairment. OBJECTIVES: To assess carriage of abnormal bacterial flora, antibiotic-resistant bacteria, infection, and mortality in children with cerebral palsy (CP) admitted for pediatric intensive care. DESIGN: Prospective observational single center cohort study. SETTING: Twenty-bed regional pediatric intensive care unit (PICU) in a university-affiliated tertiary referral children's hospital. PATIENTS: All children with an established diagnosis of CP admitted to PICU and ventilated for four or more days during a 6-yr period. MEASUREMENTS: Surveillance samples of throat and rectum were taken at admission to PICU and twice a week thereafter. Diagnostic samples were obtained on clinical indication. MAIN RESULTS: Fifty-three children with a total of 77 admissions were included. Most (90%) of the children with CP had moderate to severe functional limitations. Eighty-nine percent of the children with CP (47/53) carried abnormal bacterial flora/potential pathogens, most frequently Pseudomonas and Klebsiella species. Forty-seven percent (22/47) had antibiotic-resistant bacteria. Thirty-five children (66%) developed 86 infections during their PICU admission. Lower airways and blood were the two most commonly infected sites-Pseudomonas aeruginosa and coagulase-negative Staphylococci, the predominant infecting microorganisms. Sixty-five percent (56/86) of infections were primary endogenous infections, 21% (18/86) exogenous, and 9% (8/86) secondary endogenous. Carriage of abnormal bacterial flora, antibiotic-resistant bacteria, and infection rate was significantly higher than that of children of comparative age without CP ventilated for four or more days on PICU. Nine (17%) of the children with CP died in PICU and 4 of the deaths were infection related. CONCLUSIONS: In children with moderate to severe chronic neurologic impairment admitted to PICU, there is a high rate of carriage of abnormal bacteria/potential pathogens, antibiotic-resistant bacteria, and infection.

Imaging of brown tumours: a pictorial review.

Brown tumours do not represent neoplastic process, but they are focal bony lesions due to bone remodelling from either primary or secondary hyperparathyroidism. Their incidence is also low. The current literature on brown tumour is mainly in the form of case reports that focus on single affected sites. This pictorial review describes the full imaging workup and pathway of suspected brown tumour in the setting of both primary and secondary hyperparathyroidism. It aims to illustrate the management strategy to aid both clinicians and radiologists in suspected cases of brown tumour. We highlight the complementary roles that different imaging modalities can play in different settings including the importance of parathyroid ultrasound, 99mTc-sestamibi scintigraphy and SPECT/CT in the localisation of the parathyroid adenoma. We present cases with full clinical and imaging workup in both the acute and chronic setting and scenarios that require exclusion of primary and secondary bone malignancies.

Ultrasonography of thyroid nodules: a pictorial review.

UNLABELLED: Thyroid nodules are a common occurrence in the general population, and these incidental thyroid nodules are often referred for ultrasound (US) evaluation. US provides a safe and fast method of examination. It is sensitive for the detection of thyroid nodules, and suspicious features can be used to guide further investigation/management decisions. However, given the financial burden on the health service and unnecessary anxiety for patients, it is unrealistic to biopsy every thyroid nodule to confirm diagnosis. The British Thyroid Association (BTA) has recently produced a US classification (U1-U5) of thyroid nodules to facilitate the decision-making process regarding the need to perform fine-needle aspiration cytology (FNAC) for suspicious cases. In this pictorial review, we provide a complete series of sonographic images to illustrate benign and malignant features of thyroid nodules according to the U1-5 classification. Specifically, we highlight morphologic characteristic of the nodule, including its echo signal in relation to its consistency, nodular size, number and contour. Additional diagnostic features such as halo, colloid, calcification and vascular patterns are also discussed in detail. The aim is to assist radiologists and clinicians in recognising sonographic patterns of benign, suspicious and malignant nodules based on U1-5 criteria, and in planning for further investigations. MAIN MESSAGES: • Ultrasound is sensitive in identifying suspicious features, which require aspiration. • Whether nodules require aspiration should be based on sonographic features and clinical findings. • U1-5 classification of sonographic findings can help determine whether aspiration is necessary.

High mortality of invasive pneumococcal disease compared with meningococcal disease in critically ill children.

OBJECTIVE: To ascertain outcome, patterns of disease, incidence of concurrent infection, superinfection and penicillin resistance in children requiring intensive care for Streptococcus pneumoniae infection and compare it to a similar disease pattern, namely Neisseria meningitidis b infection. DESIGN AND SETTING: Prospective cohort study in a regional paediatric intensive care unit (PICU). PATIENTS AND PARTICIPANTS: Children with invasive pneumococcal and meningococcal disease requiring intensive care. MEASUREMENTS AND RESULTS: The study included 22 children with invasive pneumococcal disease (IPD), median age 14 months (interquartile range 3-52), median Paediatric Index of Mortality (PIM) 0.051 (0.028-0.066), median length of PICU stay 8.5 days (4-13). Four patients died, three (13.5%) attributable to IPD. Incidence of concurrent infection 27%. There were no superinfections. All S. pneumoniae were sensitive to cefotaxime; one isolate (3.7%) was resistant to penicillin. There were 186 children with meningococcal disease (MD), with a higher PIM (median 0.068, 0.033-0.108), older age (29 months, 10.7-77.9) and shorter length of PICU stay (median 3 days, 2-6). Eight (4.3%) children died from MD. Incidence of concurrent and superinfection was 18% and 6%, respectively in children with MD. All N. meningitidis cases were sensitive to cefotaxime and penicillin. The standardized mortality ratio was considerably higher with IPD (2.0) than with MD (0.52). CONCLUSIONS: In invasive pneumococcal disease preventative measures including early recognition, immediate antibiotic therapy and vaccination need to be taken in the community, similar to the control of meningococcal disease. Invasive pneumococcal disease should command the same respect as meningococcal disease.