Echocardiographic Strain to Predict Need for Transplant or Mortality in Fontan Patients with Hypoplastic Left Heart Syndrome.

Despite recent advances, hypoplastic left heart syndrome (HLHS) patients subsequent to the Fontan still have significant morbidity and mortality. Some require heart transplant due to systemic ventricular dysfunction. Limited data exist on timing for transplant referral. This study aims to correlate systemic ventricular strain by echocardiography to transplant-free survival. HLHS patients who had Fontan palliation at our institution were included. Patients were divided into: 1) Required transplant or experienced mortality (composite end point); 2) Did not require transplant or survived. For those who experienced the composite endpoint, the last echocardiogram prior to the composite outcome was used, while for those who did not experience the composite endpoint the last echocardiogram obtained was used. Several qualitative and quantitative parameters were analyzed with focus on strain parameters. Ninety-five patients with HLHS Fontan palliation were identified. Sixty-six had adequate images and eight (12%) experienced transplant or mortality. These patients had greater myocardial performance index by flow Doppler (0.72 versus 0.53, p = 0.01), higher systolic/diastolic duration ratio (1.51 versus 1.13, p = 0.02), lower fractional area change (17.65 versus 33.99, p < 0.01), lower global longitudinal strain (GLS) (-8.63 versus - 17.99, p < 0.01), lower global longitudinal strain rate (GLSR) (- 0.51 versus - 0.93, p < 0.01), lower global circumferential strain (GCS) (-6.68 versus -18.25, p < 0.01), and lower (GCSR) global circumferential strain rate (-0.45 versus -1.01, p < 0.01). ROC analysis demonstrated predictive value for GLS - 7.6 (71% sensitive, 97% specific, AUC 81%), GLSR -0.58 (71% sensitive, 88% specific, AUC 82%), GCS - 10.0 (86% sensitive, 91% specific, AUC 82%), and GCSR -0.85 (100% sensitive, 71% specific, AUC 90%). GLS and GCS can help predict transplant-free survival in patients with hypoplastic left heart syndrome having undergone Fontan palliation. Higher strain values (closer to zero) may be a helpful tool in determining when transplant evaluation is warranted in these patients.

Comparison of Quantitative Versus Qualitative Assessment of Single Right Ventricular Function for the Prediction of Midterm Outcomes.

Multiple studies have shown that quantitative evaluation of right ventricular (RV) systolic function in children with hypoplastic left heart syndrome (HLHS) is associated with outcomes. However, the most widely used method is qualitative, or subjective echocardiographic evaluation. Tricuspid annular displacement (TMAD) is a quantitative method and has been shown to be associated with transplant/death in a cohort of pediatric patients with HLHS. In this study, the same echocardiograms used in the quantitative TMAD study were qualitatively evaluated to see if the assessment correlated with midterm outcomes. We hypothesized that TMAD measures would outperform qualitative measurements. A previously published retrospective study of patients with systemic right ventricle demonstrated that TMAD measurements of function prior to the Glenn procedure were associated with midterm mortality/transplant (mean TMAD 12.4% for survivors and 10.0% for non-survivors/transplant, p = 0.03). Echocardiographic images used in that study were re-evaluated using qualitative assessment of function. A score between severely depressed (0) and supra-normal (7) was assigned independently by three cardiologists. A chart review included short-term clinical outcome measures in addition to midterm mortality/transplant. Spearman correlations and logistic regression were used to estimate the associations between function scores and clinical outcomes. Function scores were measured with acceptable inter- and intra-rater reliabilities in 47 patients who had echocardiograms used in the prior analysis before their bidirectional Glenn. The mean functional score was 5.3 ± 1.32 in survivors and 5.0 ± 1.02 in non-survivors/transplant. Subjective echocardiographic scores of function were not predictive of mortality (p = 0.23). Scores were correlated with length of cardiac intensive care unit stay (Spearman's rho = - 0.31, p = 0.04), but not post-Glenn total length of hospital stay (p = 0.4). A sub-analysis was performed for each individual operator. Only one of three operators produced scores with a significant association with mortality/transplant (p = 0.01, p = 0.25, p = 0.22, respectively). Averaged subjective measurement of function by three pediatric cardiologists in children with single right ventricle prior to the Glenn procedure was not associated with midterm outcomes. Previous work based on the same echocardiograms showed that quantitative analysis was associated with midterm outcomes. This suggests quantitative analysis may be more useful in prognostication. Future studies could confirm these results and identify which quantitative methods are most helpful.

Added Value of Live 3-Dimensional Transesophageal Echocardiography During Procedures in Fontan Patients.

3D transesophageal echocardiography (3D-TEE) has proven useful and accurate during some operating room (OR), interventional cardiac catheterization (Cath), and electrophysiologic (EP) procedures. The use of 3D-TEE during similar procedures in patients who have undergone Fontan surgery and its additional value have not been previously reported. To determine if live 3D-TEE during procedures post Fontan has added value, 3D-TEEs in 58 post-Fontan patients over a 5-year study period were reviewed. Additional information provided by 3D-TEE (over 2D-TEE) was classified into the following: A: new information which changed/refined the plan and 0: no new important information. Pre- and post-bypass OR 3D-TEEs were counted as one study. A total of 67 3D-TEEs (41 Cath, 13 OR, and 13 EP procedures) were performed. Median age was 14 years (6-39 years). Median weight was 47 kg (21-109 kg). In Cath procedures, only 2/41 (5%) were graded A (R to L atrial level shunt [Fontan leak], n = 1; thrombus in pulmonary artery stump, n = 1). In the OR, 6/13 (46%) were graded A (atrioventricular valvuloplasty, n = 1; neo-aortic valvuloplasty, n = 1; relief of systemic and pulmonary venous outflow obstruction, n = 2 and n = 2; respectively). In EP procedures, 4/13 (31%) were graded A (thrombus, n = 3; mapping for lead placement to assist in multisite pacing for dyssynchrony, n = 1). 3D-TEE of Fontan improved visualization and frequently added value in the OR/EP lab and may be helpful in select catheterization cases. Future studies with a larger sample could build on this data to identify when 3D-TEE will be most useful.

Comparison of Semi-Automated Versus Manual Quantitative Right Ventricular Assessment in Hypoplastic Left Heart Syndrome.

Quantitative echocardiographic evaluation is important for systemic right ventricles, but its asymmetric shape makes this challenging and time consuming when performed manually. Semi-automated software could make these quantitative measures easier to accomplish in the clinical setting. We hypothesized that semi-automated software would approximate manual measures of right ventricular size and function. Children with hypoplastic left heart who had echocardiograms were prospectively identified. These measurements were performed using manual and semi-automated techniques: end-diastolic and end-systolic area, fractional area change (FAC), dimensions (longitudinal, basal and mid-cavitary diameters), and tricuspid annular plane systolic excursion (TAPSE). Agreement between measures was evaluated. Sixty-three echocardiograms were analyzed. Intra- and inter-observer reliability was acceptable and similar between methods except that inter-observer reliability for the manual method was superior for TAPSE. Correlation between methods was high (r > 0.9, p < 0.001) for most of the measures. Correlation for FAC was r = 0.79, and for TAPSE the correlation was r = 0.61 (both p < 0.001). The percent relative difference between manual and semi-automated methods was less than 6% for most measures. End-systolic area and FAC had a relative difference of 10% and 11% respectively. The only measure with substantial bias between the manual and semi-automated methods was TAPSE which had a relative difference of 52%. EchoInsight® semi-automated software provides similar measures of right ventricular dimensions and FAC in patients with hypoplastic left heart compared to manual measures. Measures of TAPSE do not correlate well between manual and semi-automated methods. Further research is warranted on the use of semi-automated analyses in this patient population.

Higher order genomic organization and epigenetic control maintain cellular identity and prevent breast cancer.

Cells establish and sustain structural and functional integrity of the genome to support cellular identity and prevent malignant transformation. In this review, we present a strategic overview of epigenetic regulatory mechanisms including histone modifications and higher order chromatin organization (HCO) that are perturbed in breast cancer onset and progression. Implications for dysfunctions that occur in hormone regulation, cell cycle control, and mitotic bookmarking in breast cancer are considered, with an emphasis on epithelial-to-mesenchymal transition and cancer stem cell activities. The architectural organization of regulatory machinery is addressed within the contexts of translating cancer-compromised genomic organization to advances in breast cancer risk assessment, diagnosis, prognosis, and identification of novel therapeutic targets with high specificity and minimal off target effects.

Right Ventricular Mechanical Dyssynchrony in Hypoplastic Left Heart Syndrome: Correlation with Systolic Function and QRS Duration.

The single right ventricle (RV) in hypoplastic left heart syndrome (HLHS) often develops systolic dysfunction with time and this affects prognosis. Mechanical dyssynchrony has been reported in HLHS but has not consistently correlated with systolic function or electrical dyssynchrony. The aims of this study were to assess the relationship between RV mechanical dyssynchrony, RV systolic function, and QRS duration on surface electrocardiography. We hypothesized that surface QRS duration would not be an adequate indicator of mechanical dyssynchrony compared with dyssynchrony parameters. Retrospective analysis of echocardiograms of patients with HLHS divided into preserved vs reduced RV function. We measured two RV function parameters: (1) fractional area change (FAC) and (2) global longitudinal strain (RVGLS). We measured two dyssynchrony parameters: (1) the standard deviation of the time to peak strain for 9 segments (tPS-9) and (2) time difference between the earliest and latest time to peak strain (RV dyssynchrony index or RVDI) both corrected for R-R interval. We also measured the QRS duration from surface EKG. Mechanical dyssynchrony parameters were compared to both RV systolic function and to QRS duration. 41 patients with HLHS were identified: 21 had preserved function and 20 had reduced function defined by a FAC < 35%. The reduced function group had a significantly lower mean FAC and RVGLS. RVDI was higher in the dysfunction group and had a modest correlation with FAC (r = 0.48) and RVGLS (r = 0.57). tPS-9 was longer in the dysfunction group and had a modest correlation with FAC (r = 0.45) and RVGLS (r = 0.57). QRS duration was longer in the dysfunction group and had a modest correlation with FAC (r = 0.56) and RVGLS (r = 0.56). The weakest correlations were between QRS duration and tPS-9 (r = 0.32) and QRS duration and RVDI (r = 0.10). RV dysfunction measured by FAC was associated with mechanical dyssynchrony measured by increased RVDI and tPS-9. QRS duration was longer in the group with dysfunction but did not correlate with directly measured mechanical dyssynchrony. This may have potential implications for cardiac resynchronization therapy in univentricular patients as assessed by mechanical dyssynchrony parameters rather than QRS duration alone.

Saline Contrast Transesophageal Echocardiography in Fontan Patients: Assessment of the Presence, Type, and Size of Right to Left Shunts.

Right to left (R-L) shunts resulting in cyanosis or systemic embolization occur after the Fontan procedure. The primary modality of diagnosing these is angiography. Successful delineation of these shunts in Fontan patients using selective saline contrast transesophageal echocardiography (SCTEE) may allow for reduced radiation and contrast exposure. We hypothesized that SCTEE could accurately determine the presence, type, and semiquantitative shunt size of R-L shunts in Fontan patients. SCTEE was performed in Fontan patients undergoing angiography for clinical indications. Injections were performed in six sites: mid-Fontan, right and left pulmonary arteries, superior and inferior vena cavae, and innominate vein. R-L shunt size was subjectively graded as 0 = absent, 1 = small, and 2 = medium or large based on echo contrast density in the left atrium. SCTEE was compared to angiography. 33 patients with Fontan were studied with median age 15 years, median weight 50.1 kg, and median O2 saturation of 90% in the R-L shunt group and 95% in the no R-L shunt group. R-L shunt types included intracardiac shunts (ICS), veno-venous collaterals (VVCs), arteriovenous malformations (AVMs), and their combinations. SCTEE versus angiography results were the same for the presence, type, and size of R-L shunts in 79% (26/33). SCTEE identified shunts in 88% (29/33). Angiography identified shunts in 85% (28/33). Neither method missed any medium or large R-L shunts. SCTEE and angiography had similar accuracy. SCTEE accurately detected the presence, type, and size of R-L shunts in most Fontan patients in this study. This can be used to guide targeted angiography, reducing radiation exposure and contrast load.

Stability of dobutamine in continuous ambulatory delivery devices.

WHAT IS KNOWN AND OBJECTIVE: Continuous infusion of dobutamine plays an important role in the management of patients with end-stage heart failure. Home infusion of dobutamine using a continuous ambulatory delivery device (CADD) facilitates the management of patients in their home, avoiding complications associated with long-term hospitalization. However, the stability of dobutamine in CADD is currently unknown. Therefore, this study investigated the physicochemical stability of dobutamine in CADDs at three different temperatures over various time points. METHODS: Six CADDs (three containing dobutamine 10 mg/mL in 0.9% sodium chloride and three containing dobutamine 10 mg/mL in 5% glucose) were prepared and stored at 4°C for 7 days, followed by 12 hours at 35°C and then for another 12 hours at 25°C. An aliquot (n = 3) was withdrawn aseptically at 0, 24, 48, 72, 96, 120, 144 and 168 hours when stored at 4°C, and at 0, 6 and 12 hours when stored at the other two temperatures. Each sample was analysed for dobutamine concentration using a stability-indicating high-performance liquid chromatography. All the samples were also evaluated for change in pH, colour and for particle content. RESULTS AND DISCUSSION: No evidence of particle formation, colour or pH change was observed throughout the study period. Dobutamine, when admixed with 0.9% sodium chloride or 5% glucose, was found to be chemically stable for at least 168 hours at 4°C and for another 12 hours at 35°C and for another 12 hours at 25°C. WHAT IS NEW AND CONCLUSIONS: Our findings will allow health professionals to provide a weekly supply of dobutamine-containing CADDs to patients for home infusions. Continuous infusion over a 24-hour period using one CADD per day will also decrease the number of exchanges required and thus reduce the risk of catheter-related bloodstream infections.

Right Ventricular Systolic Function Parameters in Hypoplastic Left Heart Syndrome.

Assessment of the systolic function of the right ventricle (RV) in patients with hypoplastic left heart syndrome (HLHS) is important. The asymmetric shape and heavy trabeculations make accurate assessment of RV systolic function challenging. Novel measures of RV function could be helpful in distinguishing reduced versus preserved function in HLHS and may also be worse in HLHS with preserved function compared to normal controls. These novel methods offer promise, but research and clinical applicability is hindered as no cut-off values for normal function have been established. We performed a retrospective comparison of functional assessments from echocardiograms of HLHS patients with preserved and reduced RV function along with a control group of normal patients. Measures of function included fractional area change (FAC), tissue motion annular displacement of the tricuspid (TMAD-TV) and pulmonary valves (TMAD-PV), myocardial performance index (MPI), tricuspid tissue Doppler S' velocity, and RV global longitudinal strain (RVGLS). Comparisons were made between three groups: normal patients, HLHS with preserved function, and HLHS with reduced function defined as FAC < 35%. FAC was chosen as the reference as it is a historical standard. 41 HLHS patients were studied. Of these patients, 20 had HLHS with reduced function, and 21 had preserved function. They were compared with 27 age-matched, normal, controls. Comparison between HLHS and normal controls: in HLHS with preserved RV systolic function, compared to normal controls, tissue Doppler S', MPI, and TMAD-TV were all abnormal (all p < 0.05). RVGLS was not statistically different (20.5 ± 3.6% for normal vs. 17.9 ± 2.6% for HLHS with preserved function). TMAD-PV was similar between groups (16.1 ± 4.6% vs. 16.7 ± 5.1%). All measures were significantly worse (all p < 0.05) in the HLHS with reduced function group compared to normal controls. Comparison between HLHS preserved vs reduced function: in HLHS with reduced function defined by FAC < 35%, all measures were significantly worse compared to HLHS with preserved function (all p < 0.05). The cut-off values that correspond to a FAC of > 35% were 14.5% for TMAD-TV and 16% for RVGLS. All measures except RVGLS and TMAD-PV estimated worse function than controls even for HLHS with preserved function. Each of the functional measures was able to identify preserved vs reduced function in HLHS with FAC as the reference standard. Cut-off values between preserved and reduced function in HLHS were estimated for TMAD-TV and RVGLS based on a relatively small cohort. These cut-off values will aid in the research design of future studies.

Right Ventricular Longitudinal Shortening Before and After Stage I Surgical Palliation Correlates with Outcomes.

Quantification of right ventricular function is difficult, but important, in patients with single ventricles. Tissue motion annular displacement (TMAD) is an echocardiographic tool that measures displacement of the tricuspid valve relative to the apex. We evaluated TMAD, lateral annular displacement (LAD), and fractional area change (FAC) for correlation with outcomes. We measured TMAD, LAD, FAC, and other variables that may affect prognosis in patients with single right ventricle physiology pre- and post-Stage I palliation and correlated them with outcomes up to the Glenn procedure. Intra- and inter-observer variability for TMAD measurements were 2.7% (1.2-3.5%) and 6.1% (3.3-8.1%), respectively. Sixty-six subjects met the inclusion criteria. Pre-Stage I TMAD was 13.7% (SD 3.9%). TMAD had a linear relationship with FAC (r2 = 0.76). There was a correlation between TMAD and hospital stay (p = 0.044) and ECMO/arrest (p = 0.024). LAD correlated with ECMO/arrest (p = 0.045) and mortality/transplant (p = 0.049). FAC correlated with in-hospital mortality (p = 0.028). Post-Stage I TMAD was 11.8% (SD 3.7%). TMAD, LAD, and FAC all correlated with in-hospital mortality and mortality/transplant. In multivariate models, TMAD was independently predictive of weight for age Z score pre-Glenn. TMAD, FAC, and LAD correlate with clinically significant outcomes after the first-stage palliation. TMAD correlated with more outcomes than FAC and was the only measure that was independently predictive of any outcome. TMAD is a reproducible measure of RV function in this population. TMAD has prognostic value before and after first-stage palliation and may outperform more traditional measures.

Gemella bergeri infective endocarditis: a case report and brief review of literature.

Gemella is a genus of Gram-positive bacteria found in the digestive tract of humans. They rarely cause systemic illness but have been recently implicated in several serious infections. We report infective endocarditis caused by Gemella bergeri in a 23-year-old with a bicuspid aortic valve status post-intervention in infancy.

Prothrombotic markers in Thalassemia major patients: A paradigm shift.

BACKGROUND: It is being increasingly recognised that thalassemia major patients, like intermedia, have increased propensity for thromboembolism. Deficiency of natural anticoagulants is more recently defined finding contributing to the hypercoagulable state. The aim this study is to determine natural anticoagulants levels and their correlation with maternal characteristics, haematological and biochemical markers. METHODS: This is a prospective case-control study. We registered 80 patients and 60 healthy controls from Jan 2009 to Dec 2013. Complete blood counts, prothrombin time, activated partial thromboplastin time, protein C, protein S, antithrombin, serum ferritin, liver enzymes; HbsAg and Anti- HCV were evaluated. RESULT: There were 42 males and 38 females with mean age of 12.30±5.50 years. The mean protein C, protein S and antithrombin in patients and control were 58.25±22.5 versus 110.67±22.60, 67.90±19.58 versus 98.70±21.54 and 89.73±18.09 versus 104.0±10.98 (p<0.001) respectively. Protein C was predominantly deficient in 65% followed by protein S and antithrombin in 35% and 20% respectively. Protein C deficiency divulged positive correlation with protein S deficiency (p = 0.035) and antithrombin deficiency with hemoglobin of ≤8gm% (p<0.0025). No significant correlation of prothrombotic markers was established with maternal characteristics, hepatic dysfunction, hepatitis and serum ferritin. CONCLUSION: Substantial decrement in prothrombotic markers, primarily protein C, may be implicated in elevated thrombosis; however follow-up data is required to establish definitive thromboembolic events.

Prime-boost using separate oncolytic viruses in combination with checkpoint blockade improves anti-tumour therapy.

The anti-tumour effects associated with oncolytic virus therapy are mediated significantly through immune-mediated mechanisms, which depend both on the type of virus and the route of delivery. Here, we show that intra-tumoral oncolysis by Reovirus induced the priming of a CD8+, Th1-type anti-tumour response. By contrast, systemically delivered Vesicular Stomatitis Virus expressing a cDNA library of melanoma antigens (VSV-ASMEL) promoted a potent anti-tumour CD4+ Th17 response. Therefore, we hypothesised that combining the Reovirus-induced CD8+ T cell response, with the VSV-ASMEL CD4+ Th17 helper response, would produce enhanced anti-tumour activity. Consistent with this, priming with intra-tumoral Reovirus, followed by an intra-venous VSV-ASMEL Th17 boost, significantly improved survival of mice bearing established subcutaneous B16 melanoma tumours. We also show that combination of either therapy alone with anti-PD-1 immune checkpoint blockade augmented both the Th1 response induced by systemically delivered Reovirus in combination with GM-CSF, and also the Th17 response induced by VSV-ASMEL. Significantly, anti-PD-1 also uncovered an anti-tumour Th1 response following VSV-ASMEL treatment that was not seen in the absence of checkpoint blockade. Finally, the combination of all three treatments (priming with systemically delivered Reovirus, followed by double boosting with systemic VSV-ASMEL and anti-PD-1) significantly enhanced survival, with long-term cures, compared to any individual, or double, combination therapies, associated with strong Th1 and Th17 responses to tumour antigens. Our data show that it is possible to generate fully systemic, highly effective anti-tumour immunovirotherapy by combining oncolytic viruses, along with immune checkpoint blockade, to induce complementary mechanisms of anti-tumour immune responses.

Characterization of group B coxsackieviruses isolated from non-polio acute flaccid paralysis patients in Pakistan: vital assessment before polio eradication.

Pakistan is at the verge of polio eradication but isolation of non-polio enteroviruses (NPEVs) from acute flaccid paralysis (AFP) cases may result in serious or even fatal outcome. Many enteroviruses share similar symptoms and epidemiology as is the case with poliovirus and coxsackievirus (CV). The present study was designed to genetically characterize coxsackievirus B (CV-B) serotypes isolated from non-polio acute flaccid paralytic children, as well as to understand their probable role in paralysis. A total of 63 (20·1%) out of 313 stool samples during 2013 were found positive for NPEVs in rhabdomyosarcoma cells. Only 24 (38·0%) NPEVs were typed as CV-B by microneutralization assay and were further characterized by sequencing of the viral protein 1 (VP1) gene. Molecular phylogenetic analyses classified the study strains into six coxsackievirus B serotypes (coxsackievirus B1 to B6) with their respective prototype strains with evidence of epidemiological linkage and distinct clusters. Moreover, four major differences were found within the amino acid sequences of BC-loop in VP1 of CV-B strains. In conclusion, this study presented the molecular evolutionary genetic overview and distinct phylogenetic pattern of CV-B isolates from AFP cases in Pakistan, and explored the possible link between CV-B infections and AFP cases. Furthermore, our data reveal that these viruses might contribute to the incidence of paralysis in population and there is need of time to establish an enterovirus surveillance system for better understanding of epidemiological and virological characteristics of NPEV infections associated with AFP cases in the country.

Retrospective audit of antimicrobial prescribing practices for acute exacerbations of chronic obstructive pulmonary diseases in a large regional hospital.

WHAT IS KNOWN AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and mortality, and frequent exacerbations are associated with an increased risk of death, deterioration in lung function and reduced quality of life. Current Australian guidelines developed by the Lung Foundation of Australia (the COPD-X Plan) recommends the use of a short course of corticosteroids and oral antibiotics (amoxycillin or doxycycline) as part of the treatment of an AECOPD; however, it was noted that clinical practice at the study hospital had deviated from these guidelines. To evaluate the antibiotic prescribing practices in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients, and to compare the differences in clinical outcomes (primarily mean length of stay and the rate of unplanned readmissions) between patients who received broad- vs. narrow-spectrum antibiotics in a large regional hospital. METHODS: Retrospective audit of medical records for patients admitted with uncomplicated AECOPD during January-September, 2014 in a 224 acute bed regional hospital in Victoria, Australia. RESULTS AND DISCUSSION: Fifty-nine per cent of patients received broad-spectrum antibiotics (ceftriaxone), whereas only 10% of prescriptions were concordant with current Australian guideline recommendations. Patients receiving a broad-spectrum regimen were more likely to be older (74·9 vs. 69·9 years; P = 0·009), have a higher COPD severity score (i.e. BAP-65 score, 1·55 vs. 1·06; P = 0·002) and a higher CRP (59·2 vs. 25·5 mg/L; P = 0·003) on admission. The mean LOS was not significantly different between those who received ceftriaxone and those who did not (5·09 vs. 4·55 days; P = 0·47). There was no significant difference between the groups in rates of readmissions. WHAT IS NEW AND CONCLUSION: The antibiotic prescribing patterns for AECOPD in rural and regional Australian hospitals have not previously been examined in the current literature. In the study hospital, the majority of patients received broad-spectrum antibiotics in the initial treatment of AECOPD. No differences in hospital length of stay, or rate of readmission for AECOPD were observed between those who received broad- and narrow-spectrum antibiotics.

Willingness to Know the Cause of Death and Hypothetical Acceptability of the Minimally Invasive Autopsy in Six Diverse African and Asian Settings: A Mixed Methods Socio-Behavioural Study.

BACKGROUND: The minimally invasive autopsy (MIA) is being investigated as an alternative to complete diagnostic autopsies for cause of death (CoD) investigation. Before potential implementation of the MIA in settings where post-mortem procedures are unusual, a thorough assessment of its feasibility and acceptability is essential. METHODS AND FINDINGS: We conducted a socio-behavioural study at the community level to understand local attitudes and perceptions related to death and the hypothetical feasibility and acceptability of conducting MIAs in six distinct settings in Gabon, Kenya, Mali, Mozambique, and Pakistan. A total of 504 interviews (135 key informants, 175 health providers [including formal health professionals and traditional or informal health providers], and 194 relatives of deceased people) were conducted. The constructs "willingness to know the CoD" and "hypothetical acceptability of MIAs" were quantified and analysed using the framework analysis approach to compare the occurrence of themes related to acceptability across participants. Overall, 75% (379/504) of the participants would be willing to know the CoD of a relative. The overall hypothetical acceptability of MIA on a relative was 73% (366/504). The idea of the MIA was acceptable because of its perceived simplicity and rapidity and particularly for not "mutilating" the body. Further, MIAs were believed to help prevent infectious diseases, address hereditary diseases, clarify the CoD, and avoid witchcraft accusations and conflicts within families. The main concerns regarding the procedure included the potential breach of confidentiality on the CoD, the misperception of organ removal, and the incompatibility with some religious beliefs. Formal health professionals were concerned about possible contradictions between the MIA findings and the clinical pre-mortem diagnoses. Acceptability of the MIA was equally high among Christian and Islamic communities. However, in the two predominantly Muslim countries, MIA acceptability was higher in Mali than in Pakistan. While the results of the study are encouraging for the potential use of the MIA for CoD investigation in low-income settings, they remain hypothetical, with a need for confirmation with real-life MIA implementation and in populations beyond Health and Demographic Surveillance System areas. CONCLUSIONS: This study showed a high level of interest in knowing the CoD of a relative and a high hypothetical acceptability of MIAs as a tool for CoD investigation across six distinct settings. These findings anticipate potential barriers and facilitators, both at the health facility and community level, essential for local tailoring of recommendations for future MIA implementation.

Development of a fluorescent transgenic zebrafish biosensor for sensing aquatic heavy metal pollution.

We report a transgenic zebrafish (Danio rerio) designed to respond to heavy metals using a metal-responsive promoter linked to a fluorescent reporter gene (DsRed2). The metallothionein MT-Ia1 promoter containing metal-responsive elements was derived from the Asian green mussel, Perna viridis. The promoter is known to be induced by a broad spectrum of heavy metals. The promoter-reporter cassette cloned into the Tol2 transposon vector was microinjected into zebrafish embryos that were then reared to maturity. A transgene integration rate of 28 % was observed. The confirmed transgenics were mated with wild-type counterparts, and pools of F1 embryos were exposed to sub-lethal doses of Cd(2+), Cu(2+), Hg(2+), Pb(2+) and Zn(2+). The red fluorescence response of zebrafish embryos was observed 8 h post- exposure to these sub-lethal doses of heavy metals using a fluorescence microscope. Reporter expression estimated by real-time PCR revealed eightfold, sixfold and twofold increase on exposure to highest concentrations of Hg(2+), Cd(2+) and Cu(2+), while Pb(2+) and Zn(2+) had no effect. This biosensor could be a first-level screening method for confirming aquatic heavy metal bio-toxicity to eukaryotes.

Primary care referral practice, variability and socio-economic deprivation in colorectal cancer.

AIM: The reasons for pre-hospital delay of the diagnosis of cancer are multifactorial, but include a physician-related component. Urgent cancer pathways and direct-to-test approaches have been implemented, but the emergency presentation of colorectal cancer (CRC) remains little changed over recent years. We examined the variability between primary care providers in referral patterns and its effect on outcome. METHOD: A retrospective analysis was performed of a prospectively maintained database for 2009-2014 in a UK district hospital providing bowel cancer screening and tertiary rectal cancer services. RESULTS: Of 1145 CRC patients, 937 (81.8%) were diagnosed with a symptomatic cancer; 229/937 (24.4%) initially presented as an emergency. Between 44 primary care providers, emergency presentation varied between 8.3% and 57.1%. Patients of providers with high levels of emergency presentations (HV) had more advanced cancers than those of providers with medium (MV) or low levels (LV) [103/253 (40.7%), 154/461 (33.4%), 65/223 (29.1%); P = 0.025] and a lower 3-year overall survival (50.2%, 57.8%, 65.6%; P = 0.013), but with no difference in case-mix or deprivation levels. In adjusted analysis, this difference remained significant (advanced disease, OR 1.663, P = 0.011; 3-year hazard ratio 1.479, P = 0.010; comparing HV with LV). Conversely, elective suspected cancer referrals were less often used amongst diagnosed cancers [LV 136/223 (61.0%), MV 228/461 (49.5%), HV 114/253 (45.1%), P < 0.001] with limited evidence for a more selective approach in the use of the 2-week rule amongst all 2-week rule referrals [LV 136/2508 (5.4%); MV 228/4239 (5.4%); HV 115/1526 (7.8%); positive cancer diagnosis, P = 0.005]. CONCLUSION: Significant variability in emergency presentation of CRC requires local audit and examination of the reasons for delay in diagnosis and targeted measures to improve performance in non-emergency referral pathways.

Unabsorbed dura patch removed eight years after pituitary surgery.

The Codman ETHISORB Dura Patch is a synthetic, absorbable material whose absorption is complete within approximately 90 days. We report the first case of an unabsorbed Codman Dura patch, in which a patient was presented with nasal obstruction and epistaxis 8 years after pituitary surgery for Cushing's disease.